chr19-10871886-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_199141.2(CARM1):​c.184G>T​(p.Ala62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,246,394 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 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CARM1
NM_199141.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.737
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008084238).
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CARM1NM_199141.2 linkuse as main transcriptc.184G>T p.Ala62Ser missense_variant 1/16 ENST00000327064.9 NP_954592.1
CARM1NM_001370088.1 linkuse as main transcriptc.184G>T p.Ala62Ser missense_variant 1/15 NP_001357017.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CARM1ENST00000327064.9 linkuse as main transcriptc.184G>T p.Ala62Ser missense_variant 1/161 NM_199141.2 ENSP00000325690 P2Q86X55-3

Frequencies

GnomAD3 genomes
AF:
0.0000529
AC:
8
AN:
151280
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00156
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:
0.000103
AC:
1
AN:
9748
Hom.:
0
AF XY:
0.000162
AC XY:
1
AN XY:
6154
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00459
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:
0.0000201
AC:
22
AN:
1095114
Hom.:
0
Cov.:
30
AF XY:
0.0000152
AC XY:
8
AN XY:
525962
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000465
Gnomad4 SAS exome
AF:
0.0000867
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000217
Gnomad4 OTH exome
AF:
0.000141
GnomAD4 genome
AF:
0.0000529
AC:
8
AN:
151280
Hom.:
0
Cov.:
31
AF XY:
0.0000677
AC XY:
5
AN XY:
73872
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00156
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000110
ExAC
AF:
0.000144
AC:
10

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 submitterclinical testingAmbry GeneticsFeb 10, 2022The c.184G>T (p.A62S) 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 184, causing the alanine (A) at amino acid position 62 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
0.092
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
19
DANN
Benign
0.95
DEOGEN2
Benign
0.092
T;.;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.77
T;T;T
M_CAP
Uncertain
0.099
D
MetaRNN
Benign
0.0081
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.20
N;.;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.18
N;.;N
REVEL
Benign
0.045
Sift
Benign
0.56
T;.;T
Sift4G
Benign
0.64
T;T;T
Polyphen
0.0030
B;.;.
Vest4
0.028
MutPred
0.30
Gain of glycosylation at A62 (P = 0.0171);Gain of glycosylation at A62 (P = 0.0171);Gain of glycosylation at A62 (P = 0.0171);
MVP
0.25
MPC
1.2
ClinPred
0.023
T
GERP RS
-1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.082
gMVP
0.099

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.

Other links and lift over

dbSNP: rs761503923; hg19: chr19-10982562; COSMIC: COSV105890264; COSMIC: COSV105890264; API