Variant 10-68754070-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 ENST00000265872.11(CCAR1):c.1337G>A(p.Ser446Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCAR1
ENST00000265872.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.90

Variant links:

Genes affected

CCAR1 (HGNC:24236): (cell division cycle and apoptosis regulator 1) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; nuclear receptor coactivator activity; and transcription corepressor activity. Involved in positive regulation of cell migration and positive regulation of cell population proliferation. Acts upstream of or within positive regulation of apoptotic process. Located in nuclear envelope lumen. [provided by Alliance of Genome Resources, Apr 2022]

CCAR1 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
CCAR1	NM_018237.4 linkuse as main transcript	c.1337G>A	p.Ser446Asn	missense_variant	11/25	ENST00000265872.11	NP_060707.2
CCAR1	NM_001282959.2 linkuse as main transcript	c.1292G>A	p.Ser431Asn	missense_variant	10/24		NP_001269888.1
CCAR1	NM_001282960.2 linkuse as main transcript	c.1292G>A	p.Ser431Asn	missense_variant	10/24		NP_001269889.1
CCAR1	NR_104262.2 linkuse as main transcript	n.1437G>A		non_coding_transcript_exon_variant	11/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR1	ENST00000265872.11 linkuse as main transcript	c.1337G>A	p.Ser446Asn	missense_variant	11/25	1	NM_018237.4	ENSP00000265872	P1	Q8IX12-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250398

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135380

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454336

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723442

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000282

Hom.:

Bravo

AF:

0.0000113

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 28, 2022

The c.1337G>A (p.S446N) alteration is located in exon 11 (coding exon 10) of the CCAR1 gene. This alteration results from a G to A substitution at nucleotide position 1337, causing the serine (S) at amino acid position 446 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;.;.;.;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;D;D;D

M_CAP

Benign

0.0075

MetaRNN

Uncertain

0.47

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

.;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.3

.;N;N;N;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0070

.;D;D;D;D;D

Sift4G

Uncertain

0.026

D;D;D;D;D;D

Polyphen

0.99, 0.99, 1.0

.;D;D;.;D;.

Vest4

0.79

MutPred

0.38

Loss of glycosylation at S446 (P = 0.0553);Loss of glycosylation at S446 (P = 0.0553);.;.;.;.;

MVP

0.67

MPC

1.6

ClinPred

0.90

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.67

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