Variant 17-76737321-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001195427.2(SRSF2):c.-161C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000451 in 975,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SRSF2
NM_001195427.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

SRSF2 (HGNC:10783): (serine and arginine rich splicing factor 2) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]

SRSF2 links:

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD11 links:

ENSG00000267168 (HGNC:):

ENSG00000267168 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BS2

High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF2	NM_001195427.2 link	c.-161C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000359995.10	NP_001182356.1	Q01130-1A0A024R8U5Q53FN0
SRSF2	NM_001195427.2 link	c.-161C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000359995.10	NP_001182356.1	Q01130-1A0A024R8U5Q53FN0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRSF2	ENST00000359995.10 link	c.-161C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5	Q01130-1
SRSF2	ENST00000359995.10 link	c.-161C>G	5_prime_UTR_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5	Q01130-1
ENSG00000267168	ENST00000587459.1 link	c.239-961G>C	intron_variant	Intron 1 of 1	5		ENSP00000466829.1	K7EN84

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD4 exome

AF:

0.0000170

AC:

AN:

823204

Hom.:

Cov.:

AF XY:

0.00000734

AC XY:

AN XY:

408738

show subpopulations

Gnomad4 AFR exome

AF:

0.000623

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000321

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000197

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.61

DANN

Benign

0.72

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over