10-46462341-C-T

Variant names:

• chr10-46462341-C-T
• rs1197874424
• NM_005972.6:c.295G>A

Variant summary

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

The NM_005972.6(NPY4R):​c.295G>A​(p.Ala99Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A99S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000062 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPY4R NM_005972.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822
• Publications: 7 publications found

Genes affected

NPY4R (HGNC:9329): (neuropeptide Y receptor Y4) Enables pancreatic polypeptide receptor activity and peptide hormone binding activity. Involved in G protein-coupled receptor signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285402 (HGNC:):

LINC00842 (HGNC:44989): (long intergenic non-protein coding RNA 842)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.18435168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005972.6. 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
	NPY4R	NM_005972.6	MANE Select	c.295G>A	p.Ala99Thr	missense	Exon 3 of 3	NP_005963.4
	NPY4R	NM_001278794.2		c.295G>A	p.Ala99Thr	missense	Exon 2 of 2	NP_001265723.1	P50391

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY4R	ENST00000374312.5	TSL:1 MANE Select	c.295G>A	p.Ala99Thr	missense	Exon 3 of 3	ENSP00000363431.1	P50391
	NPY4R	ENST00000612632.3	TSL:1	c.295G>A	p.Ala99Thr	missense	Exon 2 of 2	ENSP00000480883.1	P50391
	NPY4R	ENST00000908575.1		c.295G>A	p.Ala99Thr	missense	Exon 2 of 2	ENSP00000578634.1

Frequencies

GnomAD3 genomes AF: 0.0000688 AC: 10 AN: 145312 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000757

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000418

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.0000613

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000687 AC: 15 AN: 218396 AF XY: 0.0000854

Gnomad AFR exome AF: 0.0000665

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000174

Gnomad FIN exome AF: 0.0000527

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000143 AC: 196 AN: 1369322 Hom.: 0 Cov.: 28 AF XY: 0.000124 AC XY: 85 AN XY: 684534

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000314 AC: 1 AN: 31812

American (AMR) AF: 0.00 AC: 0 AN: 43344

Ashkenazi Jewish (ASJ) AF: 0.0000395 AC: 1 AN: 25308

East Asian (EAS) AF: 0.0000773 AC: 3 AN: 38806

South Asian (SAS) AF: 0.0000240 AC: 2 AN: 83292

European-Finnish (FIN) AF: 0.0000758 AC: 4 AN: 52756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.000168 AC: 173 AN: 1031236

Other (OTH) AF: 0.000210 AC: 12 AN: 57208

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000619 AC: 9 AN: 145428 Hom.: 0 Cov.: 25 AF XY: 0.0000282 AC XY: 2 AN XY: 70824

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000755 AC: 3 AN: 39728

American (AMR) AF: 0.00 AC: 0 AN: 14508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3330

East Asian (EAS) AF: 0.000209 AC: 1 AN: 4776

South Asian (SAS) AF: 0.00 AC: 0 AN: 4528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10162

Middle Eastern (MID) AF: 0.00360 AC: 1 AN: 278

European-Non Finnish (NFE) AF: 0.0000613 AC: 4 AN: 65222

Other (OTH) AF: 0.00 AC: 0 AN: 2008

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000522181), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.99
MetaRNN	Benign	0.18	T
PhyloP100		0.82
PROVEAN	Benign	-0.45	N
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.044	D
Vest4		0.27
gMVP		0.90

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: rs1197874424; hg19: chr10-47087078; COSMIC: COSV65398529;