4-163351120-A-C

Variant names:

• chr4-163351120-A-C
• rs138572457
• NM_006174.4:c.847A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006174.4(NPY5R):​c.847A>C​(p.Lys283Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,614,138 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: NPY5R NM_006174.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.703
• Publications: 3 publications found

Genes affected

NPY5R (HGNC:7958): (neuropeptide Y receptor Y5) The protein encoded by this gene is a receptor for neuropeptide Y and peptide YY. The encoded protein appears to be involved in regulating food intake, with defects in this gene being associated with eating disorders. Also, the encoded protein is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06816715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006174.4. 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
	NPY5R	NM_006174.4	MANE Select	c.847A>C	p.Lys283Gln	missense	Exon 4 of 4	NP_006165.1	Q15761
	NPY5R	NM_001317091.2		c.847A>C	p.Lys283Gln	missense	Exon 4 of 4	NP_001304020.1	Q15761
	NPY5R	NM_001317092.2		c.847A>C	p.Lys283Gln	missense	Exon 5 of 5	NP_001304021.1	Q15761

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY5R	ENST00000338566.8	TSL:1 MANE Select	c.847A>C	p.Lys283Gln	missense	Exon 4 of 4	ENSP00000339377.3	Q15761
	NPY5R	ENST00000506953.1	TSL:6	c.847A>C	p.Lys283Gln	missense	Exon 1 of 1	ENSP00000423474.1	Q15761
	NPY5R	ENST00000515560.1	TSL:2	c.847A>C	p.Lys283Gln	missense	Exon 4 of 4	ENSP00000423917.1	Q15761

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 41 AN: 251246 AF XY: 0.000133

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000235 AC: 344 AN: 1461808 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 147 AN XY: 727204

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.000402 AC: 18 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000286 AC: 318 AN: 1111976

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.000327 AC: 5 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000216 Hom.: 0

Bravo AF: 0.000144

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.000218

EpiControl AF: 0.000356

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	0.081
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.70
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.16
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.018	D
Polyphen		0.020	B
Vest4		0.13
MVP		0.75
MPC		0.23
ClinPred		0.032	T
GERP RS		4.5
Varity_R		0.19
gMVP		0.42
Mutation Taster		=93/7	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: rs138572457; hg19: chr4-164272272;