1-23971436-G-C

Position:

chr1-23971436-G-C

Variant summary

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

The NM_054016.4(SRSF10):c.495C>G(p.Phe165Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,607,746 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SRSF10
NM_054016.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02

Variant links:

Genes affected

SRSF10 (HGNC:16713): (serine and arginine rich splicing factor 10) This gene product is a member of the serine-arginine (SR) family of proteins, which are involved in constitutive and regulated RNA splicing. Members of this family are characterized by N-terminal RNP1 and RNP2 motifs, which are required for binding to RNA, and multiple C-terminal SR/RS repeats, which are important in mediating association with other cellular proteins. This protein interacts with the oncoprotein TLS, and abrogates the influence of TLS on adenovirus E1A pre-mRNA splicing. This gene has pseudogenes on chromosomes 4, 9, 14, 18, and 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

SRSF10 links:

SRSF10 (HGNC:):

SRSF10 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=0.15831739).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRSF10	NM_054016.4 linkuse as main transcript	c.495C>G	p.Phe165Leu	missense_variant	6/6	ENST00000492112.3	NP_473357.1	O75494-1A0A0S2Z504

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRSF10	ENST00000492112.3 linkuse as main transcript	c.495C>G	p.Phe165Leu	missense_variant	6/6	1	NM_054016.4	ENSP00000420195.1	O75494-1
SRSF10	ENST00000343255.9 linkuse as main transcript	c.492C>G	p.Phe164Leu	missense_variant	6/6	2		ENSP00000344149.4	O75494-2
SRSF10	ENST00000344989.10 linkuse as main transcript	c.491+137C>G		intron_variant		1		ENSP00000342913.5	O75494-3
SRSF10	ENST00000453840.7 linkuse as main transcript	c.488+137C>G		intron_variant		1		ENSP00000388991.3	O75494-6
SRSF10	ENST00000374452.9 linkuse as main transcript	c.491+137C>G		intron_variant		1		ENSP00000363576.5	O75494-4
SRSF10	ENST00000374453.7 linkuse as main transcript	c.488+137C>G		intron_variant		5		ENSP00000363577.3	Q5JRI1
SRSF10	ENST00000484146.6 linkuse as main transcript	c.437+414C>G		intron_variant		2		ENSP00000419813.2	O75494-5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1455608

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723946

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:

0.00000811

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.495C>G (p.F165L) alteration is located in exon 6 (coding exon 6) of the SRSF10 gene. This alteration results from a C to G substitution at nucleotide position 495, causing the phenylalanine (F) at amino acid position 165 to be replaced by a leucine (L). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Benign

0.83

DEOGEN2

Benign

0.086

.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0047

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.13

Sift

Benign

0.10

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.23

.;B

Vest4

0.54

MutPred

0.30

.;Gain of helix (P = 0.1736);

MVP

0.32

ClinPred

0.28

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.49

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over