Variant 4-90308997-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145065.2(CCSER1):c.713C>T(p.Ala238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CCSER1
NM_001145065.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.605

Variant links:

Genes affected

CCSER1 (HGNC:29349): (coiled-coil serine rich protein 1)

CCSER1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.056373626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCSER1	NM_001145065.2 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant	2/11	ENST00000509176.6	NP_001138537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCSER1	ENST00000509176.6 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant	2/11	1	NM_001145065.2	ENSP00000425040	P1	Q9C0I3-1
CCSER1	ENST00000432775.6 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant	2/8	1		ENSP00000389283		Q9C0I3-2
CCSER1	ENST00000505073.5 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant, NMD_transcript_variant	2/10	1		ENSP00000420964

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248186

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134598

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Feb 28, 2023

The c.713C>T (p.A238V) alteration is located in exon 2 (coding exon 1) of the CCSER1 gene. This alteration results from a C to T substitution at nucleotide position 713, causing the alanine (A) at amino acid position 238 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.035

Sift

Benign

0.13

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.041

B;B

Vest4

0.068

MutPred

0.11

Gain of glycosylation at S240 (P = 0.0169);Gain of glycosylation at S240 (P = 0.0169);

MVP

0.13

MPC

0.064

ClinPred

0.12

GERP RS

4.1

Varity_R

0.076

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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