16-2521013-A-T

Variant names:

• chr16-2521013-A-T
• rs912444016
• NM_001330449.2:c.250A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001330449.2(AMDHD2):​c.250A>T​(p.Thr84Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMDHD2 NM_001330449.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.176

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037293375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMDHD2	NM_001330449.2	c.250A>T	p.Thr84Ser	missense_variant	Exon 3 of 11	ENST00000293971.11	NP_001317378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMDHD2	ENST00000293971.11	c.250A>T	p.Thr84Ser	missense_variant	Exon 3 of 11	1	NM_001330449.2	ENSP00000293971.6
ENSG00000259784	ENST00000569317.1	c.109A>T	p.Thr37Ser	missense_variant	Exon 2 of 4	3		ENSP00000455561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.250A>T (p.T84S) alteration is located in exon 3 (coding exon 3) of the AMDHD2 gene. This alteration results from a A to T substitution at nucleotide position 250, causing the threonine (T) at amino acid position 84 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.5
DANN	Benign	0.66
DEOGEN2	Benign	0.19	.;T;.;.;.;.;T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.68	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.037	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.045	.;N;N;N;.;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.31	N;N;N;N;.;N;N;N
REVEL	Benign	0.016
Sift	Benign	0.67	T;T;T;T;.;T;T;T
Sift4G	Benign	0.43	T;T;T;T;.;T;T;T
Polyphen		0.0, 0.0040	.;B;B;B;.;.;.;.
Vest4		0.17, 0.25, 0.23
MutPred		0.32		.;Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);
MVP		0.055
MPC		0.61
ClinPred		0.043	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.079
gMVP		0.37

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: rs912444016; hg19: chr16-2571014;