19-3938640-C-G

Variant names:

• chr19-3938640-C-G
• rs142817100
• NM_170678.3:c.204C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_170678.3(NMRK2):​c.204C>G​(p.Thr68Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T68T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NMRK2 NM_170678.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.70
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-6.7 with no splicing effect.

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.204C>G	p.Thr68Thr	synonymous	Exon 5 of 8	NP_733778.1	Q9NPI5-1
	NMRK2	NM_001289117.2		c.219C>G	p.Thr73Thr	synonymous	Exon 5 of 8	NP_001276046.1	Q9NPI5-3
	NMRK2	NM_001375467.2		c.204C>G	p.Thr68Thr	synonymous	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.204C>G	p.Thr68Thr	synonymous	Exon 5 of 8	ENSP00000168977.1	Q9NPI5-1
	NMRK2	ENST00000593949.1	TSL:1	c.219C>G	p.Thr73Thr	synonymous	Exon 4 of 7	ENSP00000472581.1	Q9NPI5-3
	NMRK2	ENST00000968742.1		c.261C>G	p.Thr87Thr	synonymous	Exon 4 of 7	ENSP00000638801.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452320 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 721526

African (AFR) AF: 0.00 AC: 0 AN: 33176

American (AMR) AF: 0.00 AC: 0 AN: 44034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39136

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106122

Other (OTH) AF: 0.00 AC: 0 AN: 59910

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-6.7

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: rs142817100; hg19: chr19-3938638;