Variant 4-90308742-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145065.2(CCSER1):c.458G>A(p.Ser153Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CCSER1
NM_001145065.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.71

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCSER1	NM_001145065.2 linkuse as main transcript	c.458G>A	p.Ser153Asn	missense_variant	2/11	ENST00000509176.6	NP_001138537.1	Q9C0I3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCSER1	ENST00000509176.6 linkuse as main transcript	c.458G>A	p.Ser153Asn	missense_variant	2/11	1	NM_001145065.2	ENSP00000425040.1	Q9C0I3-1
CCSER1	ENST00000432775.6 linkuse as main transcript	c.458G>A	p.Ser153Asn	missense_variant	2/8	1		ENSP00000389283.2	Q9C0I3-2
CCSER1	ENST00000505073.5 linkuse as main transcript	n.458G>A		non_coding_transcript_exon_variant	2/10	1		ENSP00000420964.1	E7EUW0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000283

AC:

AN:

247688

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

134384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000374

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Sep 30, 2024

The c.458G>A (p.S153N) alteration is located in exon 2 (coding exon 1) of the CCSER1 gene. This alteration results from a G to A substitution at nucleotide position 458, causing the serine (S) at amino acid position 153 to be replaced by an asparagine (N). 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

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.90

L;L

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

D;D

Vest4

0.60

MVP

0.54

MPC

0.38

ClinPred

0.58

GERP RS

5.2

Varity_R

0.39

gMVP

0.31

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