4-56467656-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006947.4(SRP72):c.21G>T(p.Gly7Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,555,988 control chromosomes in the GnomAD database, including 35,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G7G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.19 ( 3286 hom., cov: 31)

Exomes 𝑓: 0.21 ( 31769 hom. )

Consequence

SRP72
NM_006947.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.112

Publications

13 publications found

Variant links:

Genes affected

SRP72 (HGNC:11303): (signal recognition particle 72) This gene encodes the 72 kDa subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of secretory proteins to the endoplasmic reticulum (ER). The SRP complex consists of a 7S RNA and 6 protein subunits: SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72, that are bound to the 7S RNA as monomers or heterodimers. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein. Mutations in this gene are associated with familial bone marrow failure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

SRP72 Gene-Disease associations (from GenCC):

autosomal dominant aplasia and myelodysplasia
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
acute myeloid leukemia
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

SRP72 links:

ENSG00000289393 (HGNC:):

ENSG00000289393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 4-56467656-G-T is Benign according to our data. Variant chr4-56467656-G-T is described in ClinVar as [Benign]. Clinvar id is 349114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.112 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP72	NM_006947.4 link	c.21G>T	p.Gly7Gly	synonymous_variant	Exon 1 of 19	ENST00000642900.1	NP_008878.3	O76094-1V9HWK0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1 link	c.21G>T	p.Gly7Gly	synonymous_variant	Exon 1 of 19		NM_006947.4	ENSP00000495128.1		O76094-1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29544

AN:

151828

Hom.:

3272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.231

GnomAD2 exomes

AF:

0.232

AC:

45960

AN:

197836

AF XY:

0.224

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.205

AC:

288364

AN:

1404042

Hom.:

31769

Cov.:

AF XY:

0.205

AC XY:

143168

AN XY:

697074

show subpopulations

African (AFR)

AF:

0.119

AC:

3543

AN:

29744

American (AMR)

AF:

0.451

AC:

15643

AN:

34716

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

2730

AN:

24470

East Asian (EAS)

AF:

0.208

AC:

7103

AN:

34168

South Asian (SAS)

AF:

0.253

AC:

20241

AN:

80118

European-Finnish (FIN)

AF:

0.241

AC:

12569

AN:

52164

Middle Eastern (MID)

AF:

0.198

AC:

1108

AN:

5610

European-Non Finnish (NFE)

AF:

0.197

AC:

213868

AN:

1085268

Other (OTH)

AF:

0.200

AC:

11559

AN:

57784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

11815

23630

35444

47259

59074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.195

AC:

29571

AN:

151946

Hom.:

3286

Cov.:

AF XY:

0.201

AC XY:

14955

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.122

AC:

5071

AN:

41494

American (AMR)

AF:

0.352

AC:

5377

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

430

AN:

3470

East Asian (EAS)

AF:

0.195

AC:

996

AN:

5118

South Asian (SAS)

AF:

0.260

AC:

1249

AN:

4806

European-Finnish (FIN)

AF:

0.238

AC:

2518

AN:

10562

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13252

AN:

67918

Other (OTH)

AF:

0.234

AC:

493

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1147

2294

3442

4589

5736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.173

Hom.:

1418

Bravo

AF:

0.200

Asia WGS

AF:

0.266

AC:

924

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant aplasia and myelodysplasia

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.9

(source)

DANN

Benign

0.79

PhyloP100

0.11

PromoterAI

0.084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-56467656-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over