chr20-64106098-C-T

Variant names:

• chr20-64106098-C-T
• rs370307704
• NM_005286.4:c.734G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_005286.4(NPBWR2):​c.734G>A​(p.Arg245His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,611,196 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: NPBWR2 NM_005286.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.618
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07956427).
• BP6: Variant 20-64106098-C-T is Benign according to our data. Variant chr20-64106098-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3407292.Status of the report is criteria_provided_single_submitter, 1 stars.

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.734G>A	p.Arg245His	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.734G>A	p.Arg245His	missense	Exon 2 of 2	ENSP00000508236.1	P48146
	NPBWR2	ENST00000369768.1	TSL:6	c.734G>A	p.Arg245His	missense	Exon 1 of 1	ENSP00000358783.1	P48146
	MYT1	ENST00000928401.1		c.-570+3543C>T		intron	N/A	ENSP00000598460.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000325 AC: 8 AN: 246410 AF XY: 0.0000447

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000901

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1459078 Hom.: 0 Cov.: 36 AF XY: 0.0000289 AC XY: 21 AN XY: 725824

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51350

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111560

Other (OTH) AF: 0.0000497 AC: 3 AN: 60332

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.39	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.7
DANN	Benign	0.92
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.045	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.24	N
PhyloP100		0.62
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Benign	0.35	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.040
MVP		0.70
MPC		0.30
ClinPred		0.065	T
GERP RS		-2.9
Varity_R		0.030
gMVP		0.38
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs370307704; hg19: chr20-62737451; COSMIC: COSV63899901;