dbSNP rs763130641: SRP72:p.Val9CysfsTer10 (chr4-56467653-CG-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006947.4(SRP72):c.25delG(p.Val9CysfsTer10) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000174 in 1,550,624 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V9null) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SRP72
NM_006947.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.46

Publications

3 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP72	NM_006947.4 link	c.25delG	p.Val9CysfsTer10	frameshift_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.25delG	p.Val9CysfsTer10	frameshift_variant	Exon 1 of 19		NM_006947.4	ENSP00000495128.1		O76094-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000563

AC:

AN:

195388

AF XY:

0.0000460

show subpopulations

Gnomad AFR exome

AF:

0.0000930

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000973

Gnomad NFE exome

AF:

0.0000659

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1399220

Hom.:

Cov.:

AF XY:

0.0000230

AC XY:

AN XY:

694620

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29586

American (AMR)

AF:

0.0000568

AC:

AN:

35226

Ashkenazi Jewish (ASJ)

AF:

0.0000413

AC:

AN:

24186

East Asian (EAS)

AF:

0.00

AC:

AN:

34002

South Asian (SAS)

AF:

0.0000249

AC:

AN:

80184

European-Finnish (FIN)

AF:

0.0000194

AC:

AN:

51538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.0000166

AC:

AN:

1081514

Other (OTH)

AF:

0.0000348

AC:

AN:

57408

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.306

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151404

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73924

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41202

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67900

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.5

Mutation Taster

=18/182

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs763130641

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over