chr1-70228487-T-C

Position:

• chr1-70228487-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001350610.2(SRSF11):​c.-419T>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000479 in 1,461,582 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SRSF11 NM_001350610.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

SRSF11 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09317514).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRSF11	NM_001350605.2	c.269T>C	p.Val90Ala	missense_variant	2/12	ENST00000370949.2	NP_001337534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF11	ENST00000370949.2	c.269T>C	p.Val90Ala	missense_variant	2/12	1	NM_001350605.2	ENSP00000359987.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461582 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727084

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.269T>C (p.V90A) alteration is located in exon 3 (coding exon 2) of the SRSF11 gene. This alteration results from a T to C substitution at nucleotide position 269, causing the valine (V) at amino acid position 90 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	2.1	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.73	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.29	.;B;.
Vest4		0.48
MutPred		0.24		Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);
MVP		0.12
MPC		1.0
ClinPred		0.77	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.39

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: rs760367784; hg19: chr1-70694170;