20-43460871-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF6	NM_006275.6	MANE Select	c.843T>C	p.Pro281Pro	synonymous	Exon 6 of 6	NP_006266.2
	SRSF6	NR_034009.2		n.1249T>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF6	ENST00000244020.5	TSL:1 MANE Select	c.843T>C	p.Pro281Pro	synonymous	Exon 6 of 6	ENSP00000244020.3
	ENSG00000288000	ENST00000657241.1		c.653+273T>C		intron	N/A	ENSP00000499734.1
	SRSF6	ENST00000483871.6	TSL:2	n.*703T>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000433544.1

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

GnomAD2 exomes AF: 0.840 AC: 211123 AN: 251426 AF XY: 0.826

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 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

African (AFR) AF: 0.966 AC: 32334 AN: 33480

American (AMR) AF: 0.933 AC: 41736 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 20882 AN: 26136

East Asian (EAS) AF: 0.741 AC: 29402 AN: 39700

South Asian (SAS) AF: 0.651 AC: 56118 AN: 86254

European-Finnish (FIN) AF: 0.846 AC: 45198 AN: 53420

Middle Eastern (MID) AF: 0.756 AC: 4361 AN: 5768

European-Non Finnish (NFE) AF: 0.869 AC: 966860 AN: 1112002

Other (OTH) AF: 0.843 AC: 50930 AN: 60394

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

African (AFR) AF: 0.963 AC: 39986 AN: 41526

American (AMR) AF: 0.909 AC: 13894 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2786 AN: 3472

East Asian (EAS) AF: 0.701 AC: 3613 AN: 5152

South Asian (SAS) AF: 0.648 AC: 3127 AN: 4824

European-Finnish (FIN) AF: 0.845 AC: 8945 AN: 10580

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59064 AN: 67994

Other (OTH) AF: 0.868 AC: 1830 AN: 2108

Alfa AF: 0.881 Hom.: 155205

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.0
DANN	Benign	0.65
PhyloP100		-0.013
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2235611; hg19: chr20-42089511; COSMIC: COSV108071595;