20-43458814-T-C

Variant names:

• chr20-43458814-T-C
• rs6103330
• NM_006275.6:c.256+305T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006275.6(SRSF6):​c.256+305T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 150,924 control chromosomes in the GnomAD database, including 63,751 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 0.92 (63751 hom., cov: 24)
• Consequence: SRSF6 NM_006275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.45
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.256+305T>C		intron_variant	Intron 2 of 5	ENST00000244020.5	NP_006266.2
SRSF6	NR_034009.2	n.394+305T>C		intron_variant	Intron 2 of 6
SRSF6	XM_047440372.1	c.256+305T>C		intron_variant	Intron 2 of 2		XP_047296328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5	c.256+305T>C		intron_variant	Intron 2 of 5	1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.235+305T>C		intron_variant	Intron 2 of 25			ENSP00000499734.1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 138468 AN: 150814 Hom.: 63691 Cov.: 24

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.907

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.918 AC: 138584 AN: 150924 Hom.: 63751 Cov.: 24 AF XY: 0.915 AC XY: 67326 AN XY: 73570

African (AFR) AF: 0.967 AC: 39692 AN: 41044

American (AMR) AF: 0.928 AC: 14073 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2929 AN: 3460

East Asian (EAS) AF: 0.896 AC: 4505 AN: 5026

South Asian (SAS) AF: 0.800 AC: 3780 AN: 4724

European-Finnish (FIN) AF: 0.900 AC: 9368 AN: 10408

Middle Eastern (MID) AF: 0.869 AC: 252 AN: 290

European-Non Finnish (NFE) AF: 0.903 AC: 61213 AN: 67798

Other (OTH) AF: 0.909 AC: 1903 AN: 2094

Alfa AF: 0.904 Hom.: 77392

Bravo AF: 0.923

Asia WGS AF: 0.868 AC: 3000 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.022
DANN	Benign	0.65
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6103330; hg19: chr20-42087454;