NM_006947.4:c.1640+6dupA

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_006947.4(SRP72):c.1640+6dupA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,612,326 control chromosomes in the GnomAD database, including 29 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 23 hom. )

Consequence

SRP72
NM_006947.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.187

Publications

1 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 -12 ACMG points.

BP6

Variant 4-56491573-T-TA is Benign according to our data. Variant chr4-56491573-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 349129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 542 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SRP72	NM_006947.4 link	c.1640+6dupA	splice_region_variant, intron_variant	Intron 16 of 18	ENST00000642900.1	NP_008878.3	O76094-1V9HWK0
SRP72	NM_001267722.2 link	c.1457+6dupA	splice_region_variant, intron_variant	Intron 14 of 16		NP_001254651.1	O76094-2
SRP72	NR_151856.2 link	n.1659+6dupA	splice_region_variant, intron_variant	Intron 16 of 19
SRP72	XM_024454192.2 link	c.1640+6dupA	splice_region_variant, intron_variant	Intron 16 of 16		XP_024309960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1 link	c.1640+6dupA		splice_region_variant, intron_variant	Intron 16 of 18		NM_006947.4	ENSP00000495128.1		O76094-1

Frequencies

GnomAD3 genomes

AF:

0.00357

AC:

543

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00437

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00320

AC:

800

AN:

249884

AF XY:

0.00358

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00290

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.00412

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00362

AC:

5282

AN:

1460032

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

2731

AN XY:

726226

show subpopulations

African (AFR)

AF:

0.000928

AC:

AN:

33406

American (AMR)

AF:

0.00350

AC:

156

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.00314

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.00521

AC:

448

AN:

85932

European-Finnish (FIN)

AF:

0.000693

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00381

AC:

4229

AN:

1110980

Other (OTH)

AF:

0.00365

AC:

220

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

236

473

709

946

1182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00356

AC:

542

AN:

152294

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41568

American (AMR)

AF:

0.00902

AC:

138

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00476

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00437

AC:

297

AN:

68022

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00382

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00460

EpiControl

AF:

0.00569

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2023

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SRP72: BP4, BS2 -

Autosomal dominant aplasia and myelodysplasia

Benign:2

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 28, 2016

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.19

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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