chr2-231525102-C-T

Variant names:

• chr2-231525102-C-T
• rs772996560
• NM_006056.5:c.1222G>A

Variant summary

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

The NM_006056.5(NMUR1):​c.1222G>A​(p.Val408Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V408F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NMUR1 NM_006056.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.173
• Publications: 0 publications found

Genes affected

NMUR1 (HGNC:4518): (neuromedin U receptor 1) Enables neuromedin U binding activity and neuromedin U receptor activity. Involved in several processes, including activation of phospholipase C activity; chloride transport; and second-messenger-mediated signaling. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06255552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006056.5. 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
	NMUR1	NM_006056.5	MANE Select	c.1222G>A	p.Val408Ile	missense	Exon 3 of 3	NP_006047.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMUR1	ENST00000305141.5	TSL:1 MANE Select	c.1222G>A	p.Val408Ile	missense	Exon 3 of 3	ENSP00000305877.4	Q9HB89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458736 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725454

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 85874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110314

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 32

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	0.083
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.44
DANN	Benign	0.89
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.17
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.032
Sift	Benign	0.28	T
Sift4G	Benign	0.42	T
Polyphen		0.035	B
Vest4		0.021
MutPred		0.25		Loss of disorder (P = 0.1831)
MVP		0.60
MPC		0.14
ClinPred		0.12	T
GERP RS		2.2
Varity_R		0.033
gMVP		0.16
Mutation Taster		=97/3	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: rs772996560; hg19: chr2-232389813;