Variant 19-10912229-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate

The NM_199141.2(CARM1):c.604G>T(p.Ala202Ser) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CARM1
NM_199141.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.71

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PP2

Missense variant where missense usually causes diseases, CARM1

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARM1	NM_199141.2 linkuse as main transcript	c.604G>T	p.Ala202Ser	missense_variant	5/16	ENST00000327064.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARM1	ENST00000327064.9 linkuse as main transcript	c.604G>T	p.Ala202Ser	missense_variant	5/16	1	NM_199141.2	P2	Q86X55-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150408

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000687

AC:

929

AN:

1352140

Hom.:

Cov.:

AF XY:

0.000652

AC XY:

440

AN XY:

674382

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.000495

Gnomad4 ASJ exome

AF:

0.00113

Gnomad4 EAS exome

AF:

0.00133

Gnomad4 SAS exome

AF:

0.000224

Gnomad4 FIN exome

AF:

0.00129

Gnomad4 NFE exome

AF:

0.000669

Gnomad4 OTH exome

AF:

0.000943

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

150548

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73544

Gnomad4 AFR

AF:

0.00

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

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

Aug 12, 2021

The c.604G>T (p.A202S) alteration is located in exon 5 (coding exon 5) of the CARM1 gene. This alteration results from a G to T substitution at nucleotide position 604, causing the alanine (A) at amino acid position 202 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

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.61

D;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.027

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.35

Sift

Benign

0.055

T;T

Sift4G

Uncertain

0.026

D;D

Polyphen

0.32

B;.

Vest4

0.76

MutPred

0.82

Gain of catalytic residue at L198 (P = 0.2148);Gain of catalytic residue at L198 (P = 0.2148);

MVP

0.66

MPC

2.2

ClinPred

0.93

GERP RS

2.4

Varity_R

0.46

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over