20-43460761-T-A

Position:

• chr20-43460761-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006275.6(SRSF6):​c.733T>A​(p.Ser245Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SRSF6 NM_006275.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24611863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.733T>A	p.Ser245Thr	missense_variant	6/6	ENST00000244020.5	NP_006266.2
SRSF6	NR_034009.2	n.1139T>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5	c.733T>A	p.Ser245Thr	missense_variant	6/6	1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.653+163T>A		intron_variant				ENSP00000499734.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461836 Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.733T>A (p.S245T) alteration is located in exon 6 (coding exon 6) of the SRSF6 gene. This alteration results from a T to A substitution at nucleotide position 733, causing the serine (S) at amino acid position 245 to be replaced by a threonine (T). 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	Benign	0.18
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.033	D
Polyphen		0.76	P
Vest4		0.32
MutPred		0.26		Loss of stability (P = 0.1613);
MVP		0.28
MPC		0.071
ClinPred		0.57	D
GERP RS		5.8
Varity_R		0.29
gMVP		0.50

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: rs2017572972; hg19: chr20-42089401;