20-34262857-C-G

Variant names:

• chr20-34262857-C-G
• NM_001672.3:c.186C>G

Variant summary

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

The NM_001672.3(ASIP):​c.186C>G​(p.Ile62Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASIP NM_001672.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

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]

AHCY (HGNC:343): (adenosylhomocysteinase) S-adenosylhomocysteine hydrolase belongs to the adenosylhomocysteinase family. It catalyzes the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to adenosine (Ado) and L-homocysteine (Hcy). Thus, it regulates the intracellular S-adenosylhomocysteine (SAH) concentration thought to be important for transmethylation reactions. Deficiency in this protein is one of the different causes of hypermethioninemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ENSG00000250917 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIP	NM_001672.3	c.186C>G	p.Ile62Met	missense_variant	Exon 3 of 4	ENST00000374954.4	NP_001663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000374954.4	c.186C>G	p.Ile62Met	missense_variant	Exon 3 of 4	1	NM_001672.3	ENSP00000364092.3
ASIP	ENST00000568305.5	c.186C>G	p.Ile62Met	missense_variant	Exon 3 of 4	5		ENSP00000454804.1
ENSG00000250917	ENST00000512005.1	n.148-12719G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461712 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.67	.;T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.15	T;T
Polyphen		0.99	D;D
Vest4		0.31
MutPred		0.39		Loss of methylation at K60 (P = 0.071);Loss of methylation at K60 (P = 0.071);
MVP		0.62
MPC		0.16
ClinPred		0.64	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.13

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: chr20-32850663;