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GeneBe

20-43458481-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006275.6(SRSF6):c.228T>G(p.Asp76Glu) 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)

Consequence

SRSF6
NM_006275.6 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.608
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27365103).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF6NM_006275.6 linkuse as main transcriptc.228T>G p.Asp76Glu missense_variant 2/6 ENST00000244020.5
SRSF6XM_047440372.1 linkuse as main transcriptc.228T>G p.Asp76Glu missense_variant 2/3
SRSF6NR_034009.2 linkuse as main transcriptn.366T>G non_coding_transcript_exon_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF6ENST00000244020.5 linkuse as main transcriptc.228T>G p.Asp76Glu missense_variant 2/61 NM_006275.6 P2Q13247-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

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 03, 2021The c.228T>G (p.D76E) alteration is located in exon 2 (coding exon 2) of the SRSF6 gene. This alteration results from a T to G substitution at nucleotide position 228, causing the aspartic acid (D) at amino acid position 76 to be replaced by a glutamic acid (E). 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
Uncertain
0.56
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.061
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.52
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.73
T
M_CAP
Pathogenic
0.66
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
0.99
D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.20
Sift
Benign
0.26
T
Sift4G
Benign
0.38
T
Polyphen
0.033
B
Vest4
0.32
MutPred
0.27
Gain of MoRF binding (P = 0.1166);
MVP
0.54
MPC
1.5
ClinPred
0.30
T
GERP RS
-1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.13
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-42087121; API