20-34269032-C-G

Variant names:

• chr20-34269032-C-G
• rs36093428
• NM_001672.3:c.264C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001672.3(ASIP):​c.264C>G​(p.Pro88Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,607,510 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P88P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00015 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: ASIP NM_001672.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0400
• Publications: 2 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000250917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 20-34269032-C-G is Benign according to our data. Variant chr20-34269032-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3355302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.04 with no splicing effect.
• BS2: High AC in GnomAd4 at 23 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIP	NM_001672.3	MANE Select	c.264C>G	p.Pro88Pro	synonymous	Exon 4 of 4	NP_001663.2
	ASIP	NM_001385218.1		c.264C>G	p.Pro88Pro	synonymous	Exon 4 of 4	NP_001372147.1	P42127

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIP	ENST00000374954.4	TSL:1 MANE Select	c.264C>G	p.Pro88Pro	synonymous	Exon 4 of 4	ENSP00000364092.3	P42127
	ASIP	ENST00000568305.5	TSL:5	c.264C>G	p.Pro88Pro	synonymous	Exon 4 of 4	ENSP00000454804.1	P42127
	ASIP	ENST00000962459.1		c.264C>G	p.Pro88Pro	synonymous	Exon 6 of 6	ENSP00000632518.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152216 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000169 AC: 39 AN: 231134 AF XY: 0.000142

Gnomad AFR exome AF: 0.000224

Gnomad AMR exome AF: 0.000446

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000250

Gnomad NFE exome AF: 0.0000686

Gnomad OTH exome AF: 0.00105

GnomAD4 exome AF: 0.000118 AC: 172 AN: 1455176 Hom.: 1 Cov.: 31 AF XY: 0.000127 AC XY: 92 AN XY: 723368

African (AFR) AF: 0.0000900 AC: 3 AN: 33334

American (AMR) AF: 0.000610 AC: 27 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39490

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85154

European-Finnish (FIN) AF: 0.000330 AC: 17 AN: 51468

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5752

European-Non Finnish (NFE) AF: 0.0000982 AC: 109 AN: 1109722

Other (OTH) AF: 0.0000833 AC: 5 AN: 60052

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152334 Hom.: 1 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74494

African (AFR) AF: 0.000168 AC: 7 AN: 41584

American (AMR) AF: 0.000653 AC: 10 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000138 Hom.: 1

Bravo AF: 0.000219

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	ASIP-related condition (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		0.040

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs36093428; hg19: chr20-32856838;