1-70250028-C-G

Variant names:

• chr1-70250028-C-G
• rs201258859
• NM_001350605.2:c.1099C>G

Variant summary

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

The NM_001350605.2(SRSF11):​c.1099C>G​(p.Arg367Gly) 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. 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. R367C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRSF11 NM_001350605.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

Genes affected

SRSF11 (HGNC:10782): (serine and arginine rich splicing factor 11) This gene encodes 54-kD nuclear protein that contains an arginine/serine-rich region similar to segments found in pre-mRNA splicing factors. Although the function of this protein is not yet known, structure and immunolocalization data suggest that it may play a role in pre-mRNA processing. Alternative splicing results in multiple transcript variants encoding different proteins. In addition, a pseudogene of this gene has been found on chromosome 12.[provided by RefSeq, Sep 2010]

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=0.35424966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF11	NM_001350605.2	c.1099C>G	p.Arg367Gly	missense_variant	Exon 10 of 12	ENST00000370949.2	NP_001337534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF11	ENST00000370949.2	c.1099C>G	p.Arg367Gly	missense_variant	Exon 10 of 12	1	NM_001350605.2	ENSP00000359987.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	.;T;T;T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.0099
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Uncertain	2.2	M;M;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		0.0060, 0.16	.;B;.;B
Vest4		0.53
MutPred		0.27		Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);.;.;
MVP		0.73
MPC		1.1
ClinPred		0.93	D
GERP RS		3.5
Varity_R		0.30
gMVP		0.24

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: rs201258859; hg19: chr1-70715711;