4-56467645-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006947.4(SRP72):c.10G>T(p.Gly4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SRP72
NM_006947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.688

Publications

0 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26856333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP72	NM_006947.4 link	c.10G>T	p.Gly4Cys	missense_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.10G>T	p.Gly4Cys	missense_variant	Exon 1 of 19		NM_006947.4	ENSP00000495128.1		O76094-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1407534

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29942

American (AMR)

AF:

0.00

AC:

AN:

35378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24456

East Asian (EAS)

AF:

0.0000289

AC:

AN:

34568

South Asian (SAS)

AF:

0.00

AC:

AN:

80600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5618

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086820

Other (OTH)

AF:

0.00

AC:

AN:

57892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.G4C variant (also known as c.10G>T), located in coding exon 1 of the SRP72 gene, results from a G to T substitution at nucleotide position 10. The glycine at codon 4 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;.;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.76

T;T;.;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.9

L;L;L;.

PhyloP100

0.69

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

N;N;.;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0080

D;D;.;.

Sift4G

Uncertain

0.034

D;D;.;T

Polyphen

0.98

D;.;D;.

Vest4

0.26

MutPred

0.30

Loss of disorder (P = 0.0279);Loss of disorder (P = 0.0279);Loss of disorder (P = 0.0279);Loss of disorder (P = 0.0279);

MVP

0.82

MPC

0.47

ClinPred

0.76

GERP RS

1.1

PromoterAI

-0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.19

gMVP

0.33

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over