Genetic Variant SRF:p.Ala9Val (chr6-43171682-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_003131.4(SRF):c.26C>T(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SRF
NM_003131.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Publications

1 publications found

Variant links:

Genes affected

SRF (HGNC:11291): (serum response factor) This gene encodes a ubiquitous nuclear protein that stimulates both cell proliferation and differentiation. It is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors. This protein binds to the serum response element (SRE) in the promoter region of target genes. This protein regulates the activity of many immediate-early genes, for example c-fos, and thereby participates in cell cycle regulation, apoptosis, cell growth, and cell differentiation. This gene is the downstream target of many pathways; for example, the mitogen-activated protein kinase pathway (MAPK) that acts through the ternary complex factors (TCFs). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

SRF Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SRF links:

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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=0.3390236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003131.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRF	NM_003131.4	MANE Select	c.26C>T	p.Ala9Val	missense	Exon 1 of 7	NP_003122.1	P11831

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRF	ENST00000265354.6	TSL:1 MANE Select	c.26C>T	p.Ala9Val	missense	Exon 1 of 7	ENSP00000265354.4	P11831
SRF	ENST00000922430.1		c.26C>T	p.Ala9Val	missense	Exon 1 of 8	ENSP00000592489.1
SRF	ENST00000922431.1		c.26C>T	p.Ala9Val	missense	Exon 1 of 6	ENSP00000592490.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1061498

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

502106

African (AFR)

AF:

0.00

AC:

AN:

22180

American (AMR)

AF:

0.00

AC:

AN:

8682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12864

East Asian (EAS)

AF:

0.00

AC:

AN:

24694

South Asian (SAS)

AF:

0.00

AC:

AN:

20000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4182

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

906398

Other (OTH)

AF:

0.00

AC:

AN:

41744

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.78

MutationAssessor

Benign

-0.14

PhyloP100

2.2

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.60

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Benign

0.85

Polyphen

0.0010

Vest4

0.44

MutPred

0.30

Gain of loop (P = 0.0851)

MVP

0.63

MPC

1.8

ClinPred

0.48

GERP RS

2.7

PromoterAI

-0.0078

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.27

gMVP

0.58

Mutation Taster

=87/13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over