rs765140251

Variant names:

• chr19-3942161-G-A
• rs765140251
• NM_170678.3:c.581G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3942161-G-A
• chr19-3942161-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_170678.3(NMRK2):​c.581G>A​(p.Arg194His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NMRK2 NM_170678.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.410
• Publications: 1 publications found

Genes affected

NMRK2 (HGNC:17871): (nicotinamide riboside kinase 2) Enables ribosylnicotinamide kinase activity and ribosylnicotinate kinase activity. Predicted to be involved in NAD metabolic process. Predicted to act upstream of or within negative regulation of myoblast differentiation. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289254 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056898475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170678.3. 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
	NMRK2	NM_170678.3	MANE Select	c.581G>A	p.Arg194His	missense	Exon 8 of 8	NP_733778.1	Q9NPI5-1
	NMRK2	NM_001289117.2		c.596G>A	p.Arg199His	missense	Exon 8 of 8	NP_001276046.1	Q9NPI5-3
	NMRK2	NM_001375467.2		c.509G>A	p.Arg170His	missense	Exon 6 of 6	NP_001362396.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMRK2	ENST00000168977.7	TSL:2 MANE Select	c.581G>A	p.Arg194His	missense	Exon 8 of 8	ENSP00000168977.1	Q9NPI5-1
	NMRK2	ENST00000593949.1	TSL:1	c.596G>A	p.Arg199His	missense	Exon 7 of 7	ENSP00000472581.1	Q9NPI5-3
	NMRK2	ENST00000968742.1		c.638G>A	p.Arg213His	missense	Exon 7 of 7	ENSP00000638801.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250082 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460960 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726798

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.066
DANN	Benign	0.80
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.41
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.013
Sift	Benign	0.31	T
Sift4G	Benign	0.13	T
Polyphen		0.0030	B
Vest4		0.055
MutPred		0.26		Gain of glycosylation at S198 (P = 0.0757)
MVP		0.30
MPC		0.14
ClinPred		0.042	T
GERP RS		-3.2
Varity_R		0.020
gMVP		0.20
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs765140251; hg19: chr19-3942159;