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GeneBe

20-43460223-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006275.6(SRSF6):c.572A>G(p.Tyr191Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SRSF6
NM_006275.6 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47
Variant links:
Genes affected
SRSF6 (HGNC:10788): (serine and arginine rich splicing factor 6) The protein encoded by this gene is involved in mRNA splicing and may play a role in the determination of alternative splicing. The encoded nuclear protein belongs to the splicing factor SR family and has been shown to bind with and modulate another member of the family, SFRS12. Alternative splicing results in multiple transcript variants. In addition, two pseudogenes, one on chromosome 17 and the other on the X chromosome, have been found for this gene.[provided by RefSeq, Sep 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF6NM_006275.6 linkuse as main transcriptc.572A>G p.Tyr191Cys missense_variant 4/6 ENST00000244020.5
SRSF6NR_034009.2 linkuse as main transcriptn.978A>G non_coding_transcript_exon_variant 5/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF6ENST00000244020.5 linkuse as main transcriptc.572A>G p.Tyr191Cys missense_variant 4/61 NM_006275.6 P2Q13247-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461802
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsDec 22, 2023The c.572A>G (p.Y191C) alteration is located in exon 4 (coding exon 4) of the SRSF6 gene. This alteration results from a A to G substitution at nucleotide position 572, causing the tyrosine (Y) at amino acid position 191 to be replaced by a cysteine (C). 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
0.34
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.80
D
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.20
Sift
Benign
0.10
T
Sift4G
Benign
0.13
T
Polyphen
0.99
D
Vest4
0.58
MutPred
0.29
Loss of phosphorylation at Y191 (P = 0.0753);
MVP
0.25
MPC
0.096
ClinPred
0.83
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.51

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.

Other links and lift over

dbSNP: rs2017561937; hg19: chr20-42088863; API