20-34259905-G-A

Variant names:

• chr20-34259905-G-A
• rs6059743
• NM_001672.3:c.-10-460G>A

Variant summary

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

The NM_001672.3(ASIP):​c.-10-460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,762 control chromosomes in the GnomAD database, including 28,445 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 0.58 (28445 hom., cov: 30)
• Consequence: ASIP NM_001672.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 8 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]

ENSG00000250917 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 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.-10-460G>A		intron	N/A	NP_001663.2
	ASIP	NM_001385218.1		c.-10-460G>A		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.-10-460G>A		intron	N/A	ENSP00000364092.3
	ASIP	ENST00000568305.5	TSL:5	c.-10-460G>A		intron	N/A	ENSP00000454804.1
	ENSG00000250917	ENST00000512005.1	TSL:3	n.148-9767C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87753 AN: 151646 Hom.: 28381 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.579 AC: 87872 AN: 151762 Hom.: 28445 Cov.: 30 AF XY: 0.575 AC XY: 42628 AN XY: 74170

African (AFR) AF: 0.889 AC: 36867 AN: 41448

American (AMR) AF: 0.536 AC: 8154 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1790 AN: 3462

East Asian (EAS) AF: 0.627 AC: 3225 AN: 5142

South Asian (SAS) AF: 0.397 AC: 1905 AN: 4804

European-Finnish (FIN) AF: 0.413 AC: 4347 AN: 10530

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29694 AN: 67840

Other (OTH) AF: 0.564 AC: 1188 AN: 2108

Alfa AF: 0.492 Hom.: 54638

Bravo AF: 0.603

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.40
PhyloP100		0.0020
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: rs6059743; hg19: chr20-32847711;