chr9-74984975-C-T

Variant names:

• chr9-74984975-C-T
• NM_152420.3:c.1060G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152420.3(CARNMT1):​c.1060G>A​(p.Glu354Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.20

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]

CARNMT1-AS1 (HGNC:51188): (CARNMT1 antisense RNA 1)

ACMG classification

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 rank	MANE	Protein	UniProt
CARNMT1	NM_152420.3	c.1060G>A	p.Glu354Lys	missense_variant	Exon 7 of 8	ENST00000376834.8	NP_689633.1
CARNMT1	NM_001320497.2	c.823G>A	p.Glu275Lys	missense_variant	Exon 7 of 8		NP_001307426.1
CARNMT1	NR_135282.1	n.1108G>A		non_coding_transcript_exon_variant	Exon 6 of 7
CARNMT1-AS1	NR_121183.1	n.252-6190C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARNMT1	ENST00000376834.8	c.1060G>A	p.Glu354Lys	missense_variant	Exon 7 of 8	1	NM_152420.3	ENSP00000366030.3
CARNMT1-AS1	ENST00000455609.1	n.249-6190C>T		intron_variant	Intron 2 of 4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1060G>A (p.E354K) alteration is located in exon 7 (coding exon 7) of the CARNMT1 gene. This alteration results from a G to A substitution at nucleotide position 1060, causing the glutamic acid (E) at amino acid position 354 to be replaced by a lysine (K). 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	0.93
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.63		Gain of ubiquitination at E354 (P = 0.0138);
MVP		0.16
MPC		2.5
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.68
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr9-77599891;