rs6703198

Positions:

• chr1-170147101-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001136107.2(NTMT2):​c.154+840T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,304 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.027 (83 hom., cov: 32)
• Consequence: NTMT2 NM_001136107.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0274 (4175/152304) while in subpopulation SAS AF= 0.0454 (219/4826). AF 95% confidence interval is 0.0405. There are 83 homozygotes in gnomad4. There are 1903 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 83 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTMT2	NM_001136107.2	c.154+840T>C		intron_variant		ENST00000439373.3	NP_001129579.1
NTMT2	XM_011509232.3	c.-191+840T>C		intron_variant			XP_011507534.1
NTMT2	XM_011509233.3	c.-210+840T>C		intron_variant			XP_011507535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTMT2	ENST00000439373.3	c.154+840T>C		intron_variant		1	NM_001136107.2	ENSP00000408058	P1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4172 AN: 152186 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00832

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00983

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0274 AC: 4175 AN: 152304 Hom.: 83 Cov.: 32 AF XY: 0.0255 AC XY: 1903 AN XY: 74486

Gnomad4 AFR AF: 0.00832

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00985

Gnomad4 SAS AF: 0.0454

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0387 Hom.: 53

Bravo AF: 0.0246

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.21

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: rs6703198; hg19: chr1-170116242;