20-34269032-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001672.3(ASIP):c.264C>A(p.Pro88Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 1,607,478 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P88P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0062 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0073 ( 61 hom. )

Consequence

ASIP
NM_001672.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0400

Publications

2 publications found

Variant links:

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]

ASIP links:

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

AHCY links:

ENSG00000250917 (HGNC:):

ENSG00000250917 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 20-34269032-C-A is Benign according to our data. Variant chr20-34269032-C-A is described in ClinVar as Benign. ClinVar VariationId is 775119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.04 with no splicing effect.

BS2

High AC in GnomAd4 at 941 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>A	p.Pro88Pro	synonymous	Exon 4 of 4	NP_001663.2
	ASIP	NM_001385218.1		c.264C>A	p.Pro88Pro	synonymous	Exon 4 of 4	NP_001372147.1	P42127

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00619

AC:

942

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00649

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00803

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00600

AC:

1386

AN:

231134

AF XY:

0.00608

show subpopulations

Gnomad AFR exome

AF:

0.000897

Gnomad AMR exome

AF:

0.00787

Gnomad ASJ exome

AF:

0.00781

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00606

Gnomad NFE exome

AF:

0.00802

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.00733

AC:

10672

AN:

1455148

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

5240

AN XY:

723352

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33334

American (AMR)

AF:

0.00796

AC:

352

AN:

44242

Ashkenazi Jewish (ASJ)

AF:

0.00620

AC:

161

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39490

South Asian (SAS)

AF:

0.00154

AC:

131

AN:

85152

European-Finnish (FIN)

AF:

0.00521

AC:

268

AN:

51468

Middle Eastern (MID)

AF:

0.00417

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00833

AC:

9241

AN:

1109704

Other (OTH)

AF:

0.00764

AC:

459

AN:

60050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

702

1404

2106

2808

3510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00618

AC:

941

AN:

152330

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

41584

American (AMR)

AF:

0.0143

AC:

219

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00649

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00803

AC:

546

AN:

68026

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

146

195

244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.00674

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

ASIP-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.7

(source)

DANN

Benign

0.75

PhyloP100

0.040

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over