Variant chr12-95956790-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000266736.7(AMDHD1):c.415C>A(p.Gln139Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

AMDHD1
ENST00000266736.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

AMDHD1 (HGNC:28577): (amidohydrolase domain containing 1) Predicted to enable imidazolonepropionase activity. Predicted to be involved in histidine catabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

AMDHD1 links:

AMDHD1 (HGNC:):

AMDHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066542596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMDHD1	NM_152435.3 linkuse as main transcript	c.415C>A	p.Gln139Lys	missense_variant	4/9	ENST00000266736.7	NP_689648.2	Q96NU7B3KVC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMDHD1	ENST00000266736.7 linkuse as main transcript	c.415C>A	p.Gln139Lys	missense_variant	4/9	1	NM_152435.3	ENSP00000266736.2	Q96NU7
AMDHD1	ENST00000548310.1 linkuse as main transcript	n.227C>A		non_coding_transcript_exon_variant	3/8	1		ENSP00000448632.1	H0YI62
AMDHD1	ENST00000549171.1 linkuse as main transcript	n.150C>A		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251414

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135908

show subpopulations

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:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.415C>A (p.Q139K) alteration is located in exon 4 (coding exon 4) of the AMDHD1 gene. This alteration results from a C to A substitution at nucleotide position 415, causing the glutamine (Q) at amino acid position 139 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.042

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.61

M_CAP

Benign

0.0037

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

0.60

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.27

MutPred

0.54

Gain of ubiquitination at Q139 (P = 0.0325);

MVP

0.33

MPC

0.17

ClinPred

0.028

GERP RS

4.8

Varity_R

0.12

gMVP

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over