20-43458482-C-G

Variant names:

• chr20-43458482-C-G
• rs762641128
• NM_006275.6:c.229C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006275.6(SRSF6):​c.229C>G​(p.Arg77Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000956 in 1,359,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 0.0000096 (0 hom.)
• Consequence: SRSF6 NM_006275.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1696912).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF6	NM_006275.6	MANE Select	c.229C>G	p.Arg77Gly	missense	Exon 2 of 6	NP_006266.2
	SRSF6	NR_034009.2		n.367C>G		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF6	ENST00000244020.5	TSL:1 MANE Select	c.229C>G	p.Arg77Gly	missense	Exon 2 of 6	ENSP00000244020.3	Q13247-1
	ENSG00000288000	ENST00000657241.1		c.208C>G	p.Arg70Gly	missense	Exon 2 of 26	ENSP00000499734.1	A0A590UK80
	SRSF6	ENST00000945325.1		c.229C>G	p.Arg77Gly	missense	Exon 2 of 6	ENSP00000615384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000291 AC: 3 AN: 103178 AF XY: 0.0000172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000495

Gnomad ASJ exome AF: 0.000286

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000956 AC: 13 AN: 1359490 Hom.: 0 Cov.: 33 AF XY: 0.00000745 AC XY: 5 AN XY: 671008

African (AFR) AF: 0.00 AC: 0 AN: 27400

American (AMR) AF: 0.0000310 AC: 1 AN: 32254

Ashkenazi Jewish (ASJ) AF: 0.000208 AC: 5 AN: 24090

East Asian (EAS) AF: 0.00 AC: 0 AN: 31150

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3984

European-Non Finnish (NFE) AF: 0.00000562 AC: 6 AN: 1067392

Other (OTH) AF: 0.00 AC: 0 AN: 56482

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ExAC AF: 0.0000103 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.87
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.11	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.48	N
REVEL	Uncertain	0.33
Sift	Benign	0.64	T
Sift4G	Benign	0.32	T
Polyphen		0.0050	B
Vest4		0.35
MutPred		0.39		Loss of solvent accessibility (P = 0.0329)
MVP		0.66
MPC		1.9
ClinPred		0.14	T
GERP RS		3.5
PromoterAI		-0.34	Neutral
Varity_R		0.23
gMVP		0.68
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs762641128; hg19: chr20-42087122;