Genetic Variant CCSER1:p.Asn124Ser (chr4-90308655-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001145065.2(CCSER1):c.371A>G(p.Asn124Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCSER1
NM_001145065.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.619

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=0.021250308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSER1	NM_001145065.2 link	c.371A>G	p.Asn124Ser	missense_variant	Exon 2 of 11	ENST00000509176.6	NP_001138537.1	Q9C0I3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCSER1	ENST00000509176.6 link	c.371A>G	p.Asn124Ser	missense_variant	Exon 2 of 11	1	NM_001145065.2	ENSP00000425040.1	Q9C0I3-1
CCSER1	ENST00000432775.6 link	c.371A>G	p.Asn124Ser	missense_variant	Exon 2 of 8	1		ENSP00000389283.2	Q9C0I3-2
CCSER1	ENST00000505073.5 link	n.371A>G		non_coding_transcript_exon_variant	Exon 2 of 10	1		ENSP00000420964.1	E7EUW0

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246214

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133614

show subpopulations

Gnomad AFR exome

AF:

0.000130

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000193

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.371A>G (p.N124S) alteration is located in exon 2 (coding exon 1) of the CCSER1 gene. This alteration results from a A to G substitution at nucleotide position 371, causing the asparagine (N) at amino acid position 124 to be replaced by a serine (S). 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

0.064

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.3

DANN

Benign

0.82

DEOGEN2

Benign

0.0013

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0028

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.026

Sift

Benign

0.55

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0030

B;B

Vest4

0.049

MutPred

0.20

Gain of glycosylation at T128 (P = 0.0122);Gain of glycosylation at T128 (P = 0.0122);

MVP

0.095

MPC

0.054

ClinPred

0.015

GERP RS

1.4

Varity_R

0.027

gMVP

0.022

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