rs199949963

Variant names:

• chr20-43460207-A-C
• rs199949963
• NM_006275.6:c.556A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-43460207-A-C
• chr20-43460207-A-G

Variant summary

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

The NM_006275.6(SRSF6):​c.556A>C​(p.Ser186Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
• Consequence: SRSF6 NM_006275.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49

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=0.21743298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF6	NM_006275.6	c.556A>C	p.Ser186Arg	missense_variant	Exon 4 of 6	ENST00000244020.5	NP_006266.2
SRSF6	NR_034009.2	n.962A>C		non_coding_transcript_exon_variant	Exon 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5	c.556A>C	p.Ser186Arg	missense_variant	Exon 4 of 6	1	NM_006275.6	ENSP00000244020.3
ENSG00000288000	ENST00000657241.1	c.535A>C	p.Ser179Arg	missense_variant	Exon 4 of 26			ENSP00000499734.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.12
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.027
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.23	N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.18
Sift	Benign	0.57	T
Sift4G	Benign	0.66	T
Polyphen		0.98	D
Vest4		0.34
MutPred		0.31		Loss of phosphorylation at S186 (P = 2e-04);
MVP		0.043
MPC		0.086
ClinPred		0.92	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.40

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: rs199949963; hg19: chr20-42088847;