20-43458814-T-C

Position:

• chr20-43458814-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.256+305T>C		intron_variant		ENST00000244020.5	NP_006266.2
SRSF6	XM_047440372.1	c.256+305T>C		intron_variant			XP_047296328.1
SRSF6	NR_034009.2	n.394+305T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5	c.256+305T>C		intron_variant		1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.235+305T>C		intron_variant				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

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.903

Gnomad4 OTH AF: 0.909

Alfa AF: 0.899 Hom.: 58384

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6103330; hg19: chr20-42087454;