9-74998614-C-G

Variant names:

• chr9-74998614-C-G
• rs150748197
• NM_152420.3:c.894G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152420.3(CARNMT1):​c.894G>C​(p.Glu298Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CARNMT1 NM_152420.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.745

Genes affected

CARNMT1 (HGNC:23435): (carnosine N-methyltransferase 1) The protein encoded by this gene is a methyltransferase that converts carnosine to anserine, a dipeptide found abundantly in skeletal muscle. The encoded protein can methylate other dipeptides as well. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27945745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARNMT1	NM_152420.3	c.894G>C	p.Glu298Asp	missense_variant	Exon 5 of 8	ENST00000376834.8	NP_689633.1
CARNMT1	NM_001320497.2	c.657G>C	p.Glu219Asp	missense_variant	Exon 5 of 8		NP_001307426.1
CARNMT1	XM_047422766.1	c.894G>C	p.Glu298Asp	missense_variant	Exon 5 of 6		XP_047278722.1
CARNMT1	NR_135282.1	n.942G>C		non_coding_transcript_exon_variant	Exon 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARNMT1	ENST00000376834.8	c.894G>C	p.Glu298Asp	missense_variant	Exon 5 of 8	1	NM_152420.3	ENSP00000366030.3
CARNMT1	ENST00000451153.1	c.711G>C	p.Glu237Asp	missense_variant	Exon 5 of 5	3		ENSP00000396353.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000440 AC: 1 AN: 227462 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 123422

Gnomad AFR exome AF: 0.0000636

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.894G>C (p.E298D) alteration is located in exon 5 (coding exon 5) of the CARNMT1 gene. This alteration results from a G to C substitution at nucleotide position 894, causing the glutamic acid (E) at amino acid position 298 to be replaced by an aspartic acid (D). 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	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-2.4	N;N
REVEL	Benign	0.26
Sift	Benign	0.045	D;T
Sift4G	Benign	0.12	T;.
Polyphen		0.96	D;.
Vest4		0.81
MutPred		0.66		Loss of helix (P = 0.2022);.;
MVP		0.11
MPC		0.41
ClinPred		0.93	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.76

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

Other links and lift over

dbSNP: rs150748197; hg19: chr9-77613530;