4-56467656-G-T

Position:

chr4-56467656-G-T

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

SRP72 (HGNC:):

SRP72 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr4-56467656-G-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
SRP72	NM_006947.4 linkuse as main transcript	c.21G>T	p.Gly7Gly	synonymous_variant	1/19	ENST00000642900.1	NP_008878.3	O76094-1V9HWK0
SRP72	NM_001267722.2 linkuse as main transcript	c.21G>T	p.Gly7Gly	synonymous_variant	1/17		NP_001254651.1	O76094-2
SRP72	XM_024454192.2 linkuse as main transcript	c.21G>T	p.Gly7Gly	synonymous_variant	1/17		XP_024309960.1
SRP72	NR_151856.2 linkuse as main transcript	n.40G>T		non_coding_transcript_exon_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRP72	ENST00000642900.1 linkuse as main transcript	c.21G>T	p.Gly7Gly	synonymous_variant	1/19		NM_006947.4	ENSP00000495128.1	O76094-1
SRP72	ENST00000510663.6 linkuse as main transcript	c.21G>T	p.Gly7Gly	synonymous_variant	1/17	1		ENSP00000424576.1	O76094-2
SRP72	ENST00000504757.2 linkuse as main transcript	c.21G>T	p.Gly7Gly	synonymous_variant	1/5	2		ENSP00000473576.1	R4GNC1

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

GnomAD3 exomes

AF:

0.232

AC:

45960

AN:

197836

Hom.:

6443

AF XY:

0.224

AC XY:

24645

AN XY:

109860

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 SAS exome

AF:

0.254

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

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.451

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.195

AC:

29571

AN:

151946

Hom.:

3286

Cov.:

AF XY:

0.201

AC XY:

14955

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.168

Hom.:

1181

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Autosomal dominant aplasia and myelodysplasia

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.9

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over