20-34262569-T-C

Variant names:

• chr20-34262569-T-C
• rs2424984
• NM_001672.3:c.161-263T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001672.3(ASIP):​c.161-263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,980 control chromosomes in the GnomAD database, including 11,036 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (11036 hom., cov: 32)
• Consequence: ASIP NM_001672.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 6 publications found

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]

AHCY Gene-Disease associations (from GenCC):

• hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001672.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIP	NM_001672.3	MANE Select	c.161-263T>C		intron	N/A	NP_001663.2
	ASIP	NM_001385218.1		c.161-263T>C		intron	N/A	NP_001372147.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIP	ENST00000374954.4	TSL:1 MANE Select	c.161-263T>C		intron	N/A	ENSP00000364092.3
	ASIP	ENST00000568305.5	TSL:5	c.161-263T>C		intron	N/A	ENSP00000454804.1
	ASIP	ENST00000962459.1		c.161-263T>C		intron	N/A	ENSP00000632518.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43207 AN: 151862 Hom.: 11016 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.285 AC: 43259 AN: 151980 Hom.: 11036 Cov.: 32 AF XY: 0.282 AC XY: 20939 AN XY: 74296

African (AFR) AF: 0.689 AC: 28559 AN: 41468

American (AMR) AF: 0.150 AC: 2281 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 640 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1112 AN: 5150

South Asian (SAS) AF: 0.205 AC: 987 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1304 AN: 10572

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7707 AN: 67942

Other (OTH) AF: 0.241 AC: 507 AN: 2108

Alfa AF: 0.156 Hom.: 4254

Bravo AF: 0.302

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.36
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2424984; hg19: chr20-32850375;