NM_001330449.2:c.857C>G

Variant names:

• chr16-2528375-C-G
• NM_001330449.2:c.857C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001330449.2(AMDHD2):​c.857C>G​(p.Pro286Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMDHD2 NM_001330449.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.69
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

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.857C>G	p.Pro286Arg	missense	Exon 7 of 11	NP_001317378.1	Q9Y303-1
	AMDHD2	NM_001145815.2		c.857C>G	p.Pro286Arg	missense	Exon 7 of 11	NP_001139287.1	Q9Y303-3
	AMDHD2	NM_015944.4		c.857C>G	p.Pro286Arg	missense	Exon 7 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.857C>G	p.Pro286Arg	missense	Exon 7 of 11	ENSP00000293971.6	Q9Y303-1
	AMDHD2	ENST00000302956.8	TSL:1	c.857C>G	p.Pro286Arg	missense	Exon 7 of 10	ENSP00000307481.4	Q9Y303-2
	AMDHD2	ENST00000413459.7	TSL:2	c.857C>G	p.Pro286Arg	missense	Exon 7 of 11	ENSP00000391596.3	Q9Y303-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.50	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Pathogenic	0.79
Sift	Benign	0.035	D
Sift4G	Uncertain	0.045	D
Polyphen		0.95	P
Vest4		0.80
MutPred		0.50		Gain of MoRF binding (P = 0.0049)
MVP		0.82
MPC		1.7
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.79
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr16-2578376;