rs779976517

Variant summary

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

The NM_001330449.2(AMDHD2):​c.286C>G​(p.Arg96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,060 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R96W) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

AMDHD2
NM_001330449.2 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

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>G p.Arg96Gly 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>G p.Arg96Gly missense_variant Exon 3 of 11 1 NM_001330449.2 ENSP00000293971.6 Q9Y303-1
ENSG00000259784ENST00000569317.1 linkc.145C>G p.Arg49Gly missense_variant Exon 2 of 4 3 ENSP00000455561.1 H3BQ15

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
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:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458910
Hom.:
0
Cov.:
33
AF XY:
0.00000276
AC XY:
2
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.55
.;D;.;.;.;.;T;T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.46
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
.;M;M;M;.;.;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-4.0
D;D;D;D;.;D;D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0050
D;D;D;D;.;D;D;D
Sift4G
Benign
0.12
T;T;D;D;.;T;T;T
Polyphen
0.32, 0.27, 0.88
.;B;B;P;.;.;.;.
Vest4
0.44, 0.48, 0.49
MutPred
0.68
.;Loss of stability (P = 0.0282);Loss of stability (P = 0.0282);Loss of stability (P = 0.0282);Loss of stability (P = 0.0282);Loss of stability (P = 0.0282);Loss of stability (P = 0.0282);Loss of stability (P = 0.0282);
MVP
0.51
MPC
1.5
ClinPred
0.97
D
GERP RS
4.3
Varity_R
0.53
gMVP
0.69

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