dbSNP rs201759888: SRSF5:p.Arg214Gly (chr14-69771282-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001320214.2(SRSF5):c.640C>G(p.Arg214Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SRSF5
NM_001320214.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.372

Variant links:

Genes affected

SRSF5 (HGNC:10787): (serine and arginine rich splicing factor 5) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SRSF5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19697624).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF5	NM_001320214.2 link	c.640C>G	p.Arg214Gly	missense_variant	Exon 8 of 8	ENST00000557154.6	NP_001307143.1	Q13243-1A0A024R6D8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF5	ENST00000557154.6 link	c.640C>G	p.Arg214Gly	missense_variant	Exon 8 of 8	2	NM_001320214.2	ENSP00000451088.1		Q13243-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727234

show subpopulations

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:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

T;T;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

.;.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M;M;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Benign

0.093

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.036

D;D;D;D

Polyphen

0.069

B;B;B;B

Vest4

0.46

MutPred

0.42

Gain of catalytic residue at Y212 (P = 4e-04);Gain of catalytic residue at Y212 (P = 4e-04);Gain of catalytic residue at Y212 (P = 4e-04);.;

MVP

0.13

MPC

0.13

ClinPred

0.53

GERP RS

2.4

Varity_R

0.57

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over