NM_005286.4:c.880G>A

Variant names:

• chr20-64105952-C-T
• NM_005286.4:c.880G>A

Variant summary

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

The NM_005286.4(NPBWR2):​c.880G>A​(p.Val294Ile) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: NPBWR2 NM_005286.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

NPBWR2 (HGNC:4530): (neuropeptides B and W receptor 2) The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor. The encoded protein is similar in sequence to another G protein-coupled receptor (GPR7), and it is structurally similar to opioid and somatostatin receptors. This protein binds neuropeptides B and W. This gene is intronless and is expressed primarily in the frontal cortex of the brain. [provided by RefSeq, Jul 2008]

MYT1 (HGNC:7622): (myelin transcription factor 1) The protein encoded by this gene is a member of a family of neural specific, zinc finger-containing DNA-binding proteins. The protein binds to the promoter regions of proteolipid proteins of the central nervous system and plays a role in the developing nervous system. [provided by RefSeq, Jul 2008]

MYT1 Gene-Disease associations (from GenCC):

• craniofacial microsomia

  Inheritance: AD Classification: LIMITED Submitted by: G2P

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=0.1276052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005286.4. 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
	NPBWR2	NM_005286.4	MANE Select	c.880G>A	p.Val294Ile	missense	Exon 2 of 2	NP_005277.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPBWR2	ENST00000684052.1	MANE Select	c.880G>A	p.Val294Ile	missense	Exon 2 of 2	ENSP00000508236.1	P48146
	NPBWR2	ENST00000369768.1	TSL:6	c.880G>A	p.Val294Ile	missense	Exon 1 of 1	ENSP00000358783.1	P48146
	MYT1	ENST00000928401.1		c.-570+3397C>T		intron	N/A	ENSP00000598460.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.033
Sift	Benign	0.81	T
Sift4G	Benign	0.46	T
Polyphen		0.13	B
Vest4		0.15
MutPred		0.32		Loss of catalytic residue at V294 (P = 0.0243)
MVP		0.50
MPC		0.49
ClinPred		0.66	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.16
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr20-62737305;