20-43461047-C-T

Variant names:

• chr20-43461047-C-T
• rs768696362
• NM_006275.6:c.1019C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006275.6(SRSF6):​c.1019C>T​(p.Ser340Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000628 in 1,432,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: SRSF6 NM_006275.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.1019C>T	p.Ser340Leu	missense_variant	Exon 6 of 6	ENST00000244020.5	NP_006266.2
SRSF6	NR_034009.2	n.1425C>T		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.1019C>T	p.Ser340Leu	missense_variant	Exon 6 of 6	1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.653+449C>T		intron_variant	Intron 5 of 25			ENSP00000499734.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000893 AC: 2 AN: 223986 AF XY: 0.0000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000492

Gnomad NFE exome AF: 0.00000959

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000628 AC: 9 AN: 1432186 Hom.: 0 Cov.: 33 AF XY: 0.00000845 AC XY: 6 AN XY: 710362

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 32066

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 38806

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 24120

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39444

Gnomad4 SAS exome AF: 0.0000245 AC: 2 AN: 81542

Gnomad4 FIN exome AF: 0.0000190 AC: 1 AN: 52524

Gnomad4 NFE exome AF: 0.00000455 AC: 5 AN: 1099074

Gnomad4 Remaining exome AF: 0.0000169 AC: 1 AN: 59030

GnomAD4 genome Cov.: 31

Alfa AF: 0.000398 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1019C>T (p.S340L) alteration is located in exon 6 (coding exon 6) of the SRSF6 gene. This alteration results from a C to T substitution at nucleotide position 1019, causing the serine (S) at amino acid position 340 to be replaced by a leucine (L). 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	0.54
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.92	P
Vest4		0.65
MutPred		0.35		Loss of phosphorylation at S340 (P = 0);
MVP		0.14
MPC		0.069
ClinPred		0.84	D
GERP RS		5.8
Varity_R		0.65
gMVP		0.49
Mutation Taster		=58/42	polymorphism

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: rs768696362; hg19: chr20-42089687;