19-3933234-T-G

Position:

• chr19-3933234-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_170678.3(NMRK2):​c.-215+56T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 29)
• Consequence: NMRK2 NM_170678.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMRK2	NM_170678.3	c.-215+56T>G		intron_variant		ENST00000168977.7	NP_733778.1
NMRK2	NM_001289117.2	c.-215+56T>G		intron_variant			NP_001276046.1
NMRK2	NR_110316.2	n.110+56T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMRK2	ENST00000168977.7	c.-215+56T>G		intron_variant		2	NM_170678.3	ENSP00000168977	A2
	ENST00000691552.1	n.98-390A>C		intron_variant, non_coding_transcript_variant
NMRK2	ENST00000599576.5	c.-2+56T>G		intron_variant		3		ENSP00000471436
NMRK2	ENST00000616156.4	c.-215+56T>G		intron_variant		5		ENSP00000480091	P2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.1
DANN	Benign	0.60

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: rs2304191; hg19: chr19-3933232;