rs762641128

Variant names:

• chr20-43458482-C-A
• NM_006275.6:c.229C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-43458482-C-A
• chr20-43458482-C-G
• chr20-43458482-C-T

Variant summary

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

The NM_006275.6(SRSF6):​c.229C>A​(p.Arg77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,359,488 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R77C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SRSF6 NM_006275.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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=0.3221208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.229C>A	p.Arg77Ser	missense_variant	Exon 2 of 6	ENST00000244020.5	NP_006266.2
SRSF6	XM_047440372.1	c.229C>A	p.Arg77Ser	missense_variant	Exon 2 of 3		XP_047296328.1
SRSF6	NR_034009.2	n.367C>A		non_coding_transcript_exon_variant	Exon 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5	c.229C>A	p.Arg77Ser	missense_variant	Exon 2 of 6	1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.208C>A	p.Arg70Ser	missense_variant	Exon 2 of 26			ENSP00000499734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000221 AC: 3 AN: 1359488 Hom.: 0 Cov.: 33 AF XY: 0.00000447 AC XY: 3 AN XY: 671006

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: 0.00000281

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.56	N
REVEL	Uncertain	0.31
Sift	Benign	0.71	T
Sift4G	Benign	0.49	T
Polyphen		0.059	B
Vest4		0.47
MutPred		0.46		Gain of phosphorylation at R77 (P = 0.0017);
MVP		0.67
MPC		1.7
ClinPred		0.59	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.72

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: chr20-42087122;