NM_001672.3:c.357C>T

Variant names:

• chr20-34269125-C-T
• rs768466168
• NM_001672.3:c.357C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001672.3(ASIP):​c.357C>T​(p.Phe119Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,556,916 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00045 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00068 (1 hom.)
• Consequence: ASIP NM_001672.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.722

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 20-34269125-C-T is Benign according to our data. Variant chr20-34269125-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3358009.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.722 with no splicing effect.
• BS2: High AC in GnomAd4 at 68 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIP	NM_001672.3	c.357C>T	p.Phe119Phe	synonymous_variant	Exon 4 of 4	ENST00000374954.4	NP_001663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000374954.4	c.357C>T	p.Phe119Phe	synonymous_variant	Exon 4 of 4	1	NM_001672.3	ENSP00000364092.3
ASIP	ENST00000568305.5	c.357C>T	p.Phe119Phe	synonymous_variant	Exon 4 of 4	5		ENSP00000454804.1
ENSG00000250917	ENST00000512005.1	n.147+11902G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152246 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000964

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000373 AC: 57 AN: 152620 Hom.: 0 AF XY: 0.000398 AC XY: 33 AN XY: 82826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000776

Gnomad NFE exome AF: 0.000748

Gnomad OTH exome AF: 0.000468

GnomAD4 exome AF: 0.000678 AC: 953 AN: 1404670 Hom.: 1 Cov.: 31 AF XY: 0.000660 AC XY: 458 AN XY: 693670

Gnomad4 AFR exome AF: 0.0000630

Gnomad4 AMR exome AF: 0.0000541

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.0000277

Gnomad4 SAS exome AF: 0.0000375

Gnomad4 FIN exome AF: 0.000728

Gnomad4 NFE exome AF: 0.000804

Gnomad4 OTH exome AF: 0.000654

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152246 Hom.: 1 Cov.: 31 AF XY: 0.000430 AC XY: 32 AN XY: 74388

Gnomad4 AFR AF: 0.0000964

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000734 Hom.: 0

Bravo AF: 0.000412

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ASIP-related condition Benign:1

Jul 21, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.96

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

LitVar

Other links and lift over

dbSNP: rs768466168; hg19: chr20-32856931;