Variant 6-89098939-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080743.5(SRSF12):c.425A>C(p.His142Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,611,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

SRSF12
NM_080743.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

SRSF12 (HGNC:21220): (serine and arginine rich splicing factor 12) Enables RNA binding activity. Involved in mRNA 5'-splice site recognition and regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in cytoplasm and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

SRSF12 links:

PM20D2 (HGNC:):

PM20D2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF12	NM_080743.5 linkuse as main transcript	c.425A>C	p.His142Pro	missense_variant	5/5	ENST00000452027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SRSF12	ENST00000452027.3 linkuse as main transcript	c.425A>C	p.His142Pro	missense_variant	5/5	1	NM_080743.5	P1
SRSF12	ENST00000488604.1 linkuse as main transcript	n.691A>C		non_coding_transcript_exon_variant	3/3	2
SRSF12	ENST00000524221.1 linkuse as main transcript	n.707A>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000129

AC:

AN:

247478

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134312

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000292

AC:

426

AN:

1459504

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

725920

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000368

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000223

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000269

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.425A>C (p.H142P) alteration is located in exon 5 (coding exon 5) of the SRSF12 gene. This alteration results from a A to C substitution at nucleotide position 425, causing the histidine (H) at amino acid position 142 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Benign

0.94

DEOGEN2

Benign

0.013

Eigen

Benign

-0.048

Eigen_PC

Benign

0.077

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.56

M_CAP

Benign

0.0046

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.76

MutationTaster

Benign

0.84

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.4

REVEL

Benign

0.11

Sift

Uncertain

0.0030

Sift4G

Benign

0.28

Polyphen

0.68

Vest4

0.35

MVP

0.35

MPC

0.82

ClinPred

0.051

GERP RS

3.8

Varity_R

0.21

gMVP

0.44

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

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