20-43458481-T-G

Position:

• chr20-43458481-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006275.6(SRSF6):​c.228T>G​(p.Asp76Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRSF6 NM_006275.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.608

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27365103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.228T>G	p.Asp76Glu	missense_variant	2/6	ENST00000244020.5	NP_006266.2
SRSF6	XM_047440372.1	c.228T>G	p.Asp76Glu	missense_variant	2/3		XP_047296328.1
SRSF6	NR_034009.2	n.366T>G		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5	c.228T>G	p.Asp76Glu	missense_variant	2/6	1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.207T>G	p.Asp69Glu	missense_variant	2/26			ENSP00000499734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Dec 03, 2021

The c.228T>G (p.D76E) alteration is located in exon 2 (coding exon 2) of the SRSF6 gene. This alteration results from a T to G substitution at nucleotide position 228, causing the aspartic acid (D) at amino acid position 76 to be replaced by a glutamic acid (E). 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	0.56
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Benign	0.26	T
Sift4G	Benign	0.38	T
Polyphen		0.033	B
Vest4		0.32
MutPred		0.27		Gain of MoRF binding (P = 0.1166);
MVP		0.54
MPC		1.5
ClinPred		0.30	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-42087121;