chr20-34262885-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001672.3(ASIP):​c.214T>A​(p.Ser72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ASIP
NM_001672.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.238
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1948039).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASIPNM_001672.3 linkc.214T>A p.Ser72Thr missense_variant Exon 3 of 4 ENST00000374954.4 NP_001663.2 P42127

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASIPENST00000374954.4 linkc.214T>A p.Ser72Thr missense_variant Exon 3 of 4 1 NM_001672.3 ENSP00000364092.3 P42127
ASIPENST00000568305.5 linkc.214T>A p.Ser72Thr missense_variant Exon 3 of 4 5 ENSP00000454804.1 P42127
ENSG00000250917ENST00000512005.1 linkn.148-12747A>T intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.27
T;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.75
.;T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.87
N;N
REVEL
Benign
0.088
Sift
Benign
0.065
T;T
Sift4G
Benign
0.62
T;T
Polyphen
0.61
P;P
Vest4
0.19
MutPred
0.32
Gain of methylation at K70 (P = 0.1036);Gain of methylation at K70 (P = 0.1036);
MVP
0.41
MPC
0.58
ClinPred
0.49
T
GERP RS
0.40
Varity_R
0.20
gMVP
0.14

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1455904899; hg19: chr20-32850691; API