19-3938694-C-G

Variant names:

• chr19-3938694-C-G
• rs144718564
• NM_170678.3:c.258C>G

Variant summary

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

The NM_170678.3(NMRK2):​c.258C>G​(p.Ser86Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,210 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S86S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: NMRK2 NM_170678.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• 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: 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=0.070108026).

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.258C>G	p.Ser86Arg	missense	Exon 5 of 8	NP_733778.1	Q9NPI5-1
	NMRK2	NM_001289117.2		c.273C>G	p.Ser91Arg	missense	Exon 5 of 8	NP_001276046.1	Q9NPI5-3
	NMRK2	NM_001375467.2		c.258C>G	p.Ser86Arg	missense	Exon 4 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.258C>G	p.Ser86Arg	missense	Exon 5 of 8	ENSP00000168977.1	Q9NPI5-1
	NMRK2	ENST00000593949.1	TSL:1	c.273C>G	p.Ser91Arg	missense	Exon 4 of 7	ENSP00000472581.1	Q9NPI5-3
	NMRK2	ENST00000968742.1		c.315C>G	p.Ser105Arg	missense	Exon 4 of 7	ENSP00000638801.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460210 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726350

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111288

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.91
DANN	Benign	0.89
DEOGEN2	Benign	0.042	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-1.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.014
Sift	Benign	0.090	T
Sift4G	Benign	0.11	T
Polyphen		0.31	B
Vest4		0.14
MutPred		0.27		Loss of helix (P = 0.028)
MVP		0.28
MPC		0.13
ClinPred		0.12	T
GERP RS		-0.92
Varity_R		0.071
gMVP		0.51
Mutation Taster		=98/2	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: rs144718564; hg19: chr19-3938692;