1-70228487-T-G

Variant names:

• chr1-70228487-T-G
• rs760367784
• NM_001350605.2:c.269T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350605.2(SRSF11):​c.269T>G​(p.Val90Gly) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V90A) 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: 6.66

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039679497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF11	NM_001350605.2	c.269T>G	p.Val90Gly	missense_variant	Exon 2 of 12	ENST00000370949.2	NP_001337534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF11	ENST00000370949.2	c.269T>G	p.Val90Gly	missense_variant	Exon 2 of 12	1	NM_001350605.2	ENSP00000359987.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.050	.;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.2	N;N;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	4.5	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.95	T;T;T
Polyphen		0.0020	.;B;.
Vest4		0.33
MutPred		0.32		Loss of stability (P = 0.0148);Loss of stability (P = 0.0148);Loss of stability (P = 0.0148);
MVP		0.043
MPC		1.1
ClinPred		0.24	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs760367784; hg19: chr1-70694170;