Variant 12-119102244-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_194286.4(SRRM4):c.140C>T(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,612,528 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 14 hom. )

Consequence

SRRM4
NM_194286.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

SRRM4 (HGNC:29389): (serine/arginine repetitive matrix 4) SRRM4 promotes alternative splicing and inclusion of neural-specific exons in target mRNAs (Calarco et al., 2009 [PubMed 19737518]).[supplied by OMIM, Oct 2009]

SRRM4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004866749).

BP6

Variant 12-119102244-C-T is Benign according to our data. Variant chr12-119102244-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3234197.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRM4	NM_194286.4 linkuse as main transcript	c.140C>T	p.Pro47Leu	missense_variant	2/13	ENST00000267260.5	NP_919262.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRRM4	ENST00000267260.5 linkuse as main transcript	c.140C>T	p.Pro47Leu	missense_variant	2/13	1	NM_194286.4	ENSP00000267260	P1
	ENST00000537730.1 linkuse as main transcript	n.75+14643G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

380

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000851

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00373

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00224

AC:

555

AN:

248220

Hom.:

AF XY:

0.00208

AC XY:

280

AN XY:

134662

show subpopulations

Gnomad AFR exome

AF:

0.000582

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000651

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.00516

GnomAD4 exome

AF:

0.00356

AC:

5202

AN:

1460322

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

2433

AN XY:

726494

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00308

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00431

Gnomad4 OTH exome

AF:

0.00314

GnomAD4 genome

AF:

0.00250

AC:

380

AN:

152206

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00537

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000851

Gnomad4 NFE

AF:

0.00373

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00267

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00366

AC:

ExAC

AF:

0.00230

AC:

278

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00295

EpiControl

AF:

0.00346

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

SRRM4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.12

Eigen_PC

Benign

0.035

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.62

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.99

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.80

REVEL

Benign

0.045

Sift

Benign

0.58

Sift4G

Benign

0.38

Polyphen

0.073

Vest4

0.36

MVP

0.15

MPC

0.15

ClinPred

0.0094

GERP RS

3.9

Varity_R

0.067

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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