chr16-2521049-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330449.2(AMDHD2):​c.286C>T​(p.Arg96Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,611,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

AMDHD2
NM_001330449.2 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85
Variant links:
Genes affected
AMDHD2 (HGNC:24262): (amidohydrolase domain containing 2) Enables N-acetylglucosamine-6-phosphate deacetylase activity. Predicted to be involved in N-acetylglucosamine catabolic process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AMDHD2NM_001330449.2 linkc.286C>T p.Arg96Trp missense_variant Exon 3 of 11 ENST00000293971.11 NP_001317378.1 Q9Y303-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMDHD2ENST00000293971.11 linkc.286C>T p.Arg96Trp missense_variant Exon 3 of 11 1 NM_001330449.2 ENSP00000293971.6 Q9Y303-1
ENSG00000259784ENST00000569317.1 linkc.145C>T p.Arg49Trp missense_variant Exon 2 of 4 3 ENSP00000455561.1 H3BQ15

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152150
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248808
Hom.:
0
AF XY:
0.00000744
AC XY:
1
AN XY:
134434
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000617
AC:
9
AN:
1458910
Hom.:
0
Cov.:
33
AF XY:
0.00000827
AC XY:
6
AN XY:
725528
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:
0.00000810
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152150
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.286C>T (p.R96W) alteration is located in exon 3 (coding exon 3) of the AMDHD2 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a tryptophan (W). 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
0.22
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.68
.;D;.;.;.;.;T;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.65
D;D;D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.0
.;M;M;M;.;.;.;.
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-4.8
D;D;D;D;.;D;D;D
REVEL
Benign
0.20
Sift
Uncertain
0.0010
D;D;D;D;.;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;.;D;D;D
Polyphen
0.99, 0.98, 1.0
.;D;D;D;.;.;.;.
Vest4
0.32, 0.35, 0.49
MutPred
0.72
.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP
0.46
MPC
1.7
ClinPred
0.94
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.70
gMVP
0.80

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: rs779976517; hg19: chr16-2571050; API