Variant 12-95966442-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000266736.7(AMDHD1):c.1127A>G(p.Lys376Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 ( 0 hom. )

Consequence

AMDHD1
ENST00000266736.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

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:

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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=0.07122642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMDHD1	NM_152435.3 linkuse as main transcript	c.1127A>G	p.Lys376Arg	missense_variant	8/9	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.1127A>G	p.Lys376Arg	missense_variant	8/9	1	NM_152435.3	ENSP00000266736.2	Q96NU7
AMDHD1	ENST00000548310.1 linkuse as main transcript	n.*606A>G		non_coding_transcript_exon_variant	7/8	1		ENSP00000448632.1	H0YI62
AMDHD1	ENST00000548310.1 linkuse as main transcript	n.*606A>G		3_prime_UTR_variant	7/8	1		ENSP00000448632.1	H0YI62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jul 13, 2022

The c.1127A>G (p.K376R) alteration is located in exon 8 (coding exon 8) of the AMDHD1 gene. This alteration results from a A to G substitution at nucleotide position 1127, causing the lysine (K) at amino acid position 376 to be replaced by an arginine (R). 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

0.070

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.036

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.012

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.6

MutationTaster

Benign

0.56

PrimateAI

Benign

0.41

PROVEAN

Benign

0.64

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MutPred

0.58

Gain of catalytic residue at K376 (P = 0);

MVP

0.63

MPC

0.11

ClinPred

0.14

GERP RS

4.7

Varity_R

0.091

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over