NM_005972.6:c.295G>T

Variant names:

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

Variant summary

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

The NM_005972.6(NPY4R):​c.295G>T​(p.Ala99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (15 hom., cov: 25)
  • Exomes 𝑓: 0.25 (21 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPY4R NM_005972.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22038004).
• BP6: Variant 10-46462341-C-A is Benign according to our data. Variant chr10-46462341-C-A is described in ClinVar as Benign. ClinVar VariationId is 768356.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T	p.Ala99Ser	missense	Exon 3 of 3	NP_005963.4
	NPY4R	NM_001278794.2		c.295G>T	p.Ala99Ser	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>T	p.Ala99Ser	missense	Exon 3 of 3	ENSP00000363431.1	P50391
	NPY4R	ENST00000612632.3	TSL:1	c.295G>T	p.Ala99Ser	missense	Exon 2 of 2	ENSP00000480883.1	P50391
	NPY4R	ENST00000908575.1		c.295G>T	p.Ala99Ser	missense	Exon 2 of 2	ENSP00000578634.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 32130 AN: 129680 Hom.: 15 Cov.: 25

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.233

GnomAD2 exomes AF: 0.270 AC: 58942 AN: 218396 AF XY: 0.270

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.337

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.217

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.266

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.245 AC: 296225 AN: 1207646 Hom.: 21 Cov.: 28 AF XY: 0.248 AC XY: 149367 AN XY: 602138

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

African (AFR) AF: 0.251 AC: 7158 AN: 28564

American (AMR) AF: 0.333 AC: 12639 AN: 37972

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 5724 AN: 21604

East Asian (EAS) AF: 0.212 AC: 7683 AN: 36238

South Asian (SAS) AF: 0.348 AC: 24803 AN: 71266

European-Finnish (FIN) AF: 0.238 AC: 11149 AN: 46772

Middle Eastern (MID) AF: 0.289 AC: 1405 AN: 4868

European-Non Finnish (NFE) AF: 0.234 AC: 212972 AN: 910078

Other (OTH) AF: 0.252 AC: 12692 AN: 50284

⚠️ 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: InbreedingCoeff AF: 0.248 AC: 32162 AN: 129782 Hom.: 15 Cov.: 25 AF XY: 0.250 AC XY: 15837 AN XY: 63382

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

African (AFR) AF: 0.251 AC: 9015 AN: 35958

American (AMR) AF: 0.299 AC: 3856 AN: 12916

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 778 AN: 2928

East Asian (EAS) AF: 0.197 AC: 873 AN: 4434

South Asian (SAS) AF: 0.352 AC: 1418 AN: 4030

European-Finnish (FIN) AF: 0.223 AC: 2030 AN: 9112

Middle Eastern (MID) AF: 0.270 AC: 67 AN: 248

European-Non Finnish (NFE) AF: 0.235 AC: 13525 AN: 57584

Other (OTH) AF: 0.236 AC: 425 AN: 1800

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.99
MetaRNN	Benign	0.22	T
PhyloP100		0.82
PROVEAN	Benign	-1.4	N
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.013	D
Vest4		0.26
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: COSV65398480;