20-43460871-T-C

Variant names:

• chr20-43460871-T-C
• rs2235611
• NM_006275.6:c.843T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006275.6(SRSF6):​c.843T>C​(p.Pro281Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 1,614,018 control chromosomes in the GnomAD database, including 595,363 homozygotes. 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 0.88 (59672 hom., cov: 30)
  • Exomes 𝑓: 0.85 (535691 hom.)
• Consequence: SRSF6 NM_006275.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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]

ENSG00000288000 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.013 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.843T>C	p.Pro281Pro	synonymous_variant	Exon 6 of 6	ENST00000244020.5	NP_006266.2
SRSF6	NR_034009.2	n.1249T>C		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5	c.843T>C	p.Pro281Pro	synonymous_variant	Exon 6 of 6	1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.653+273T>C		intron_variant	Intron 5 of 25			ENSP00000499734.1

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134157 AN: 152022 Hom.: 59598 Cov.: 30

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.866

GnomAD3 exomes AF: 0.840 AC: 211123 AN: 251426 Hom.: 89816 AF XY: 0.826 AC XY: 112231 AN XY: 135896

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.801

Gnomad EAS exome AF: 0.697

Gnomad SAS exome AF: 0.647

Gnomad FIN exome AF: 0.850

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.843

GnomAD4 exome AF: 0.854 AC: 1247821 AN: 1461878 Hom.: 535691 Cov.: 72 AF XY: 0.846 AC XY: 615585 AN XY: 727240

Gnomad4 AFR exome AF: 0.966

Gnomad4 AMR exome AF: 0.933

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.651

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.869

Gnomad4 OTH exome AF: 0.843

GnomAD4 genome AF: 0.883 AC: 134292 AN: 152140 Hom.: 59672 Cov.: 30 AF XY: 0.876 AC XY: 65121 AN XY: 74350

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.868

Alfa AF: 0.868 Hom.: 64009

Bravo AF: 0.895

Asia WGS AF: 0.715 AC: 2487 AN: 3478

EpiCase AF: 0.856

EpiControl AF: 0.856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.0
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs2235611; hg19: chr20-42089511;