Genetic Variant NM_001330449.2:c.29C>A (chr16-2520487-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001330449.2(AMDHD2):c.29C>A(p.Ala10Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000925 in 1,080,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

AMDHD2
NM_001330449.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.75

Publications

0 publications found

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]

AMDHD2 links:

ENSG00000259784 (HGNC:):

ENSG00000259784 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30081284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330449.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMDHD2	NM_001330449.2	MANE Select	c.29C>A	p.Ala10Asp	missense	Exon 1 of 11	NP_001317378.1	Q9Y303-1
AMDHD2	NM_001145815.2		c.29C>A	p.Ala10Asp	missense	Exon 1 of 11	NP_001139287.1	Q9Y303-3
AMDHD2	NM_015944.4		c.29C>A	p.Ala10Asp	missense	Exon 1 of 10	NP_057028.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMDHD2	ENST00000293971.11	TSL:1 MANE Select	c.29C>A	p.Ala10Asp	missense	Exon 1 of 11	ENSP00000293971.6	Q9Y303-1
AMDHD2	ENST00000302956.8	TSL:1	c.29C>A	p.Ala10Asp	missense	Exon 1 of 10	ENSP00000307481.4	Q9Y303-2
ENSG00000259784	ENST00000569317.1	TSL:3	c.80-497C>A		intron	N/A	ENSP00000455561.1	H3BQ15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.25e-7

AC:

AN:

1080608

Hom.:

Cov.:

AF XY:

0.00000196

AC XY:

AN XY:

510786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22416

American (AMR)

AF:

0.00

AC:

AN:

8210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13692

East Asian (EAS)

AF:

0.00

AC:

AN:

26014

South Asian (SAS)

AF:

0.00

AC:

AN:

19652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2866

European-Non Finnish (NFE)

AF:

0.00000109

AC:

AN:

914326

Other (OTH)

AF:

0.00

AC:

AN:

42898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.092

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.73

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

3.7

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.36

REVEL

Benign

0.18

Sift

Benign

0.33

Sift4G

Benign

0.31

Polyphen

0.24

Vest4

0.61

MutPred

0.54

Loss of MoRF binding (P = 0.0375)

MVP

0.14

MPC

1.2

ClinPred

0.66

GERP RS

2.7

PromoterAI

-0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.68

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over