NM_001330449.2:c.31C>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/20 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14429826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMDHD2	NM_001330449.2	c.31C>A	p.Arg11Ser	missense_variant	Exon 1 of 11	ENST00000293971.11	NP_001317378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMDHD2	ENST00000293971.11	c.31C>A	p.Arg11Ser	missense_variant	Exon 1 of 11	1	NM_001330449.2	ENSP00000293971.6
ENSG00000259784	ENST00000569317.1	c.80-495C>A		intron_variant	Intron 1 of 3	3		ENSP00000455561.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1078912 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 509946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.086	T;.;.;.;.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.68	T;T;T;T;T;T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;L;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.45	N;N;N;.;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.61	T;T;D;.;T;T;T
Sift4G	Benign	0.38	T;T;D;.;T;T;T
Polyphen		0.0	B;B;B;.;.;.;.
Vest4		0.18
MutPred		0.62		Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);
MVP		0.081
MPC		0.81
ClinPred		0.54	D
GERP RS		0.46
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

LitVar

Other links and lift over

dbSNP: rs761700526; hg19: chr16-2570490;