NM_001330449.2:c.31C>T

Variant names:

• chr16-2520489-C-T
• rs761700526
• NM_001330449.2:c.31C>T

Variant summary

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

The NM_001330449.2(AMDHD2):​c.31C>T​(p.Arg11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 1,078,912 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: AMDHD2 NM_001330449.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.972
• 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: 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=0.36514586).

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.31C>T	p.Arg11Cys	missense	Exon 1 of 11	NP_001317378.1	Q9Y303-1
	AMDHD2	NM_001145815.2		c.31C>T	p.Arg11Cys	missense	Exon 1 of 11	NP_001139287.1	Q9Y303-3
	AMDHD2	NM_015944.4		c.31C>T	p.Arg11Cys	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.31C>T	p.Arg11Cys	missense	Exon 1 of 11	ENSP00000293971.6	Q9Y303-1
	AMDHD2	ENST00000302956.8	TSL:1	c.31C>T	p.Arg11Cys	missense	Exon 1 of 10	ENSP00000307481.4	Q9Y303-2
	ENSG00000259784	ENST00000569317.1	TSL:3	c.80-495C>T		intron	N/A	ENSP00000455561.1	H3BQ15

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00 AC: 0 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 AF: 0.00000834 AC: 9 AN: 1078912 Hom.: 0 Cov.: 31 AF XY: 0.00000196 AC XY: 1 AN XY: 509946

African (AFR) AF: 0.00 AC: 0 AN: 22326

American (AMR) AF: 0.00 AC: 0 AN: 8152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13566

East Asian (EAS) AF: 0.0000386 AC: 1 AN: 25878

South Asian (SAS) AF: 0.00 AC: 0 AN: 19644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2976

European-Non Finnish (NFE) AF: 0.00000876 AC: 8 AN: 912848

Other (OTH) AF: 0.00 AC: 0 AN: 42728

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000124 AC: 1

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	0.22
BayesDel_addAF	Benign	-0.0060	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.93
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.97
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Benign	0.043	D
Sift4G	Uncertain	0.028	D
Polyphen		0.78	P
Vest4		0.20
MutPred		0.65		Loss of MoRF binding (P = 0.0016)
MVP		0.12
MPC		1.9
ClinPred		0.66	D
GERP RS		0.46
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.093
gMVP		0.60
Mutation Taster		=87/13	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: rs761700526; hg19: chr16-2570490;