chr7-24291665-T-A

Position:

• chr7-24291665-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000905.4(NPY):​c.272T>A​(p.Leu91His) variant causes a missense, splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPY NM_000905.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.36

Genes affected

NPY (HGNC:7955): (neuropeptide Y) This gene encodes a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. The neuropeptide functions through G protein-coupled receptors to inhibit adenylyl cyclase, activate mitogen-activated protein kinase (MAPK), regulate intracellular calcium levels, and activate potassium channels. A polymorphism in this gene resulting in a change of leucine 7 to proline in the signal peptide is associated with elevated cholesterol levels, higher alcohol consumption, and may be a risk factor for various metabolic and cardiovascular diseases. The protein also exhibits antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]

LOC107986777 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19885924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY	NM_000905.4	c.272T>A	p.Leu91His	missense_variant, splice_region_variant	4/4	ENST00000242152.7	NP_000896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7	c.272T>A	p.Leu91His	missense_variant, splice_region_variant	4/4	1	NM_000905.4	ENSP00000242152.2
NPY	ENST00000405982.1	c.272T>A	p.Leu91His	missense_variant, splice_region_variant	3/3	1		ENSP00000385282.1
NPY	ENST00000407573.5	c.272T>A	p.Leu91His	missense_variant, splice_region_variant	5/5	3		ENSP00000384364.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2024

The c.272T>A (p.L91H) alteration is located in exon 4 (coding exon 3) of the NPY gene. This alteration results from a T to A substitution at nucleotide position 272, causing the leucine (L) at amino acid position 91 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.60	.;.;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.16	N;N;N
REVEL	Benign	0.056
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.13	B;B;B
Vest4		0.45
MutPred		0.14		Loss of stability (P = 0.0412);Loss of stability (P = 0.0412);Loss of stability (P = 0.0412);
MVP		0.42
MPC		0.80
ClinPred		0.80	D
GERP RS		5.4
Varity_R		0.11
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-24331284;