NM_001330449.2:c.152T>C

Variant names:

• chr16-2520837-T-C
• rs966131811
• NM_001330449.2:c.152T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001330449.2(AMDHD2):​c.152T>C​(p.Val51Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,611,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: AMDHD2 NM_001330449.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063783795).

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.152T>C	p.Val51Ala	missense	Exon 2 of 11	NP_001317378.1	Q9Y303-1
	AMDHD2	NM_001145815.2		c.152T>C	p.Val51Ala	missense	Exon 2 of 11	NP_001139287.1	Q9Y303-3
	AMDHD2	NM_015944.4		c.152T>C	p.Val51Ala	missense	Exon 2 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.152T>C	p.Val51Ala	missense	Exon 2 of 11	ENSP00000293971.6	Q9Y303-1
	AMDHD2	ENST00000302956.8	TSL:1	c.152T>C	p.Val51Ala	missense	Exon 2 of 10	ENSP00000307481.4	Q9Y303-2
	ENSG00000259784	ENST00000569317.1	TSL:3	c.80-147T>C		intron	N/A	ENSP00000455561.1	H3BQ15

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151964 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459636 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726196

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000448 AC: 2 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111356

Other (OTH) AF: 0.0000331 AC: 2 AN: 60336

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.000261 AC: 4 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

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	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.53	N
PhyloP100		1.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.021
Sift	Benign	0.71	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.33		Gain of disorder (P = 0.0363)
MVP		0.23
MPC		0.81
ClinPred		0.19	T
GERP RS		1.9
PromoterAI		-0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.34

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: rs966131811; hg19: chr16-2570838;