chr1-170167576-T-C

Variant names:

• chr1-170167576-T-C
• rs1023526554
• NM_001136107.2:c.671T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136107.2(NTMT2):​c.671T>C​(p.Val224Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V224E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NTMT2 NM_001136107.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95
• Publications: 0 publications found

Genes affected

NTMT2 (HGNC:31932): (N-terminal Xaa-Pro-Lys N-methyltransferase 2) Enables N-terminal protein N-methyltransferase activity. Involved in N-terminal protein amino acid methylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2586559).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136107.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTMT2	NM_001136107.2	MANE Select	c.671T>C	p.Val224Ala	missense	Exon 4 of 4	NP_001129579.1	Q5VVY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTMT2	ENST00000439373.3	TSL:1 MANE Select	c.671T>C	p.Val224Ala	missense	Exon 4 of 4	ENSP00000408058.3	Q5VVY1
	NTMT2	ENST00000962802.1		c.623T>C	p.Val208Ala	missense	Exon 4 of 4	ENSP00000632861.1
	NTMT2	ENST00000367764.3	TSL:5	n.*13T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.9
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.13
Sift	Benign	0.063	T
Sift4G	Benign	0.15	T
Polyphen		0.13	B
Vest4		0.27
MutPred		0.74		Loss of stability (P = 0.031)
MVP		0.055
ClinPred		0.93	D
GERP RS		4.0
Varity_R		0.76
gMVP		0.57
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs1023526554; hg19: chr1-170136717;