dbSNP rs761700526: AMDHD2:p.Arg11Ser (chr16-2520489-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330449.2(AMDHD2):c.31C>A(p.Arg11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. R11C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AMDHD2
NM_001330449.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.972

Publications

1 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14429826).

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.31C>A	p.Arg11Ser	missense	Exon 1 of 11	NP_001317378.1	Q9Y303-1
AMDHD2	NM_001145815.2		c.31C>A	p.Arg11Ser	missense	Exon 1 of 11	NP_001139287.1	Q9Y303-3
AMDHD2	NM_015944.4		c.31C>A	p.Arg11Ser	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.31C>A	p.Arg11Ser	missense	Exon 1 of 11	ENSP00000293971.6	Q9Y303-1
AMDHD2	ENST00000302956.8	TSL:1	c.31C>A	p.Arg11Ser	missense	Exon 1 of 10	ENSP00000307481.4	Q9Y303-2
ENSG00000259784	ENST00000569317.1	TSL:3	c.80-495C>A		intron	N/A	ENSP00000455561.1	H3BQ15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

7618

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1078912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509946

African (AFR)

AF:

0.00

AC:

AN:

22326

American (AMR)

AF:

0.00

AC:

AN:

8152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13566

East Asian (EAS)

AF:

0.00

AC:

AN:

25878

South Asian (SAS)

AF:

0.00

AC:

AN:

19644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2976

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

912848

Other (OTH)

AF:

0.00

AC:

AN:

42728

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.086

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.97

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.45

REVEL

Benign

0.057

Sift

Benign

0.61

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.18

MutPred

0.62

Loss of MoRF binding (P = 0.0115)

MVP

0.081

MPC

0.81

ClinPred

0.54

GERP RS

0.46

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.081

gMVP

0.50

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