Variant 19-10871905-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_199141.2(CARM1):c.203G>T(p.Gly68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 1,224,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

CARM1
NM_199141.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.399

Variant links:

Genes affected

CARM1 (HGNC:23393): (coactivator associated arginine methyltransferase 1) This gene belongs to the protein arginine methyltransferase (PRMT) family. The encoded enzyme catalyzes the methylation of guanidino nitrogens of arginyl residues of proteins. The enzyme acts specifically on histones and other chromatin-associated proteins and is involved in regulation of gene expression. The enzyme may act in association with other proteins or within multi-protein complexes and may play a role in cell type-specific functions and cell lineage specification. A related pseudogene is located on chromosome 9. [provided by RefSeq, Aug 2013]

CARM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, CARM1

BP4

Computational evidence support a benign effect (MetaRNN=0.027554005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARM1	NM_199141.2 linkuse as main transcript	c.203G>T	p.Gly68Val	missense_variant	1/16	ENST00000327064.9
CARM1	NM_001370088.1 linkuse as main transcript	c.203G>T	p.Gly68Val	missense_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARM1	ENST00000327064.9 linkuse as main transcript	c.203G>T	p.Gly68Val	missense_variant	1/16	1	NM_199141.2	P2	Q86X55-3

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.000434

AC:

AN:

2304

Hom.:

AF XY:

0.000699

AC XY:

AN XY:

1430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00236

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:

0.00000466

AC:

AN:

1073742

Hom.:

Cov.:

AF XY:

0.00000585

AC XY:

AN XY:

512672

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000256

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:

0.00000219

Gnomad4 OTH exome

AF:

0.0000241

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73806

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000132

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:

0.0000340

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

Nov 29, 2023

The c.203G>T (p.G68V) alteration is located in exon 1 (coding exon 1) of the CARM1 gene. This alteration results from a G to T substitution at nucleotide position 203, causing the glycine (G) at amino acid position 68 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

-0.29

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.071

T;.;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.70

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.30

N;.;N

REVEL

Benign

0.015

Sift

Benign

0.29

T;.;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.012

B;.;.

Vest4

0.14

MutPred

0.48

Loss of disorder (P = 0.07);Loss of disorder (P = 0.07);Loss of disorder (P = 0.07);

MVP

0.11

MPC

1.6

ClinPred

0.034

GERP RS

-0.10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.15

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