rs1389635061

Variant names:

• chr16-2520487-C-T
• rs1389635061
• NM_001330449.2:c.29C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2520487-C-T
• chr16-2520487-C-A
• chr16-2520487-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330449.2(AMDHD2):​c.29C>T​(p.Ala10Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000244 in 1,230,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: AMDHD2 NM_001330449.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75
• Publications: 0 publications found

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]

ENSG00000259784 (HGNC:):

ACMG classification

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=0.29257047).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMDHD2	NM_001330449.2	MANE Select	c.29C>T	p.Ala10Val	missense	Exon 1 of 11	NP_001317378.1	Q9Y303-1
	AMDHD2	NM_001145815.2		c.29C>T	p.Ala10Val	missense	Exon 1 of 11	NP_001139287.1	Q9Y303-3
	AMDHD2	NM_015944.4		c.29C>T	p.Ala10Val	missense	Exon 1 of 10	NP_057028.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMDHD2	ENST00000293971.11	TSL:1 MANE Select	c.29C>T	p.Ala10Val	missense	Exon 1 of 11	ENSP00000293971.6	Q9Y303-1
	AMDHD2	ENST00000302956.8	TSL:1	c.29C>T	p.Ala10Val	missense	Exon 1 of 10	ENSP00000307481.4	Q9Y303-2
	ENSG00000259784	ENST00000569317.1	TSL:3	c.80-497C>T		intron	N/A	ENSP00000455561.1	H3BQ15

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149546 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1080608 Hom.: 0 Cov.: 31 AF XY: 0.00000196 AC XY: 1 AN XY: 510786

African (AFR) AF: 0.00 AC: 0 AN: 22416

American (AMR) AF: 0.00 AC: 0 AN: 8210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13692

East Asian (EAS) AF: 0.00 AC: 0 AN: 26014

South Asian (SAS) AF: 0.00 AC: 0 AN: 19652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2866

European-Non Finnish (NFE) AF: 0.00000219 AC: 2 AN: 914326

Other (OTH) AF: 0.00 AC: 0 AN: 42898

GnomAD4 genome AF: 0.00000669 AC: 1 AN: 149546 Hom.: 0 Cov.: 29 AF XY: 0.0000137 AC XY: 1 AN XY: 72898

African (AFR) AF: 0.00 AC: 0 AN: 40666

American (AMR) AF: 0.0000662 AC: 1 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67114

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.79
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.0020	B
Vest4		0.40
MutPred		0.44		Gain of relative solvent accessibility (P = 0.09)
MVP		0.067
MPC		0.73
ClinPred		0.52	D
GERP RS		2.7
PromoterAI		-0.0020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.56
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs1389635061; hg19: chr16-2570488;