19-3938694-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_170678.3(NMRK2):​c.258C>T​(p.Ser86Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00844 in 1,612,366 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (55 hom.)
• Consequence: NMRK2 NM_170678.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -12 ACMG points.

• BP6: Variant 19-3938694-C-T is Benign according to our data. Variant chr19-3938694-C-T is described in ClinVar as Benign. ClinVar VariationId is 770652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 55 AR gene

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>T	p.Ser86Ser	synonymous	Exon 5 of 8	NP_733778.1	Q9NPI5-1
	NMRK2	NM_001289117.2		c.273C>T	p.Ser91Ser	synonymous	Exon 5 of 8	NP_001276046.1	Q9NPI5-3
	NMRK2	NM_001375467.2		c.258C>T	p.Ser86Ser	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.258C>T	p.Ser86Ser	synonymous	Exon 5 of 8	ENSP00000168977.1	Q9NPI5-1
	NMRK2	ENST00000593949.1	TSL:1	c.273C>T	p.Ser91Ser	synonymous	Exon 4 of 7	ENSP00000472581.1	Q9NPI5-3
	NMRK2	ENST00000968742.1		c.315C>T	p.Ser105Ser	synonymous	Exon 4 of 7	ENSP00000638801.1

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 839 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00931

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00483 AC: 1206 AN: 249730 AF XY: 0.00497

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00457

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00841

Gnomad OTH exome AF: 0.00543

GnomAD4 exome AF: 0.00875 AC: 12770 AN: 1460078 Hom.: 55 Cov.: 32 AF XY: 0.00852 AC XY: 6188 AN XY: 726286

African (AFR) AF: 0.00132 AC: 44 AN: 33438

American (AMR) AF: 0.00459 AC: 205 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26104

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

South Asian (SAS) AF: 0.000557 AC: 48 AN: 86122

European-Finnish (FIN) AF: 0.00172 AC: 91 AN: 52926

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5762

European-Non Finnish (NFE) AF: 0.0106 AC: 11833 AN: 1111178

Other (OTH) AF: 0.00889 AC: 536 AN: 60318

GnomAD4 genome AF: 0.00551 AC: 839 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.00510 AC XY: 380 AN XY: 74460

African (AFR) AF: 0.00202 AC: 84 AN: 41562

American (AMR) AF: 0.00445 AC: 68 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00931 AC: 633 AN: 68018

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00502 Hom.: 1

Bravo AF: 0.00583

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.52
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs144718564; hg19: chr19-3938692;