rs1129414

Positions:

• chr20-34262853-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001672.3(ASIP):​c.182A>C​(p.Gln61Pro) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASIP NM_001672.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

Genes affected

ASIP (HGNC:745): (agouti signaling protein) In mice, the agouti gene encodes a paracrine signaling molecule that causes hair follicle melanocytes to synthesize pheomelanin, a yellow pigment, instead of the black or brown pigment, eumelanin. Pleiotropic effects of constitutive expression of the mouse gene include adult-onset obesity, increased tumor susceptibility, and premature infertility. This gene is highly similar to the mouse gene and encodes a secreted protein that may (1) affect the quality of hair pigmentation, (2) act as a pharmacological antagonist of alpha-melanocyte-stimulating hormone, (3) play a role in neuroendocrine aspects of melanocortin action, and (4) have a functional role in regulating lipid metabolism in adipocytes. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060323596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIP	NM_001672.3	c.182A>C	p.Gln61Pro	missense_variant	3/4	ENST00000374954.4	NP_001663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000374954.4	c.182A>C	p.Gln61Pro	missense_variant	3/4	1	NM_001672.3	ENSP00000364092	P1
	ENST00000512005.1	n.148-12715T>G		intron_variant, non_coding_transcript_variant		3
ASIP	ENST00000568305.5	c.182A>C	p.Gln61Pro	missense_variant	3/4	5		ENSP00000454804	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000118 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.20	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.092
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.22	T;T
Polyphen		0.019	B;B
Vest4		0.16
MutPred		0.14		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP		0.23
MPC		0.19
ClinPred		0.056	T
GERP RS		-4.3
Varity_R		0.31
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs1129414; hg19: chr20-32850659;