chr1-109621146-T-A

Position:

• chr1-109621146-T-A

Variant summary

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

The NM_001368809.2(AMPD2):​c.-30T>A variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPD2 NM_001368809.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.358

Genes affected

AMPD2 (HGNC:469): (adenosine monophosphate deaminase 2) The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

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=0.043701768).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD2	NM_001368809.2	c.-30T>A		5_prime_UTR_variant	2/19	ENST00000528667.7	NP_001355738.1
AMPD2	NM_001308170.1	c.39T>A	p.Thr13=	synonymous_variant	1/17		NP_001295099.1
AMPD2	NM_004037.9	c.-30T>A		5_prime_UTR_variant	1/18		NP_004028.4
AMPD2	NM_139156.4	c.10+868T>A		intron_variant			NP_631895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667.7	c.-30T>A		5_prime_UTR_variant	2/19	1	NM_001368809.2	ENSP00000436541	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.133T>A (p.S45T) alteration is located in exon 1 (coding exon 1) of the AMPD2 gene. This alteration results from a T to A substitution at nucleotide position 133, causing the serine (S) at amino acid position 45 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.32	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.12	N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0050	B;B
Vest4		0.15
MutPred		0.12		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.31
MPC		0.61
ClinPred		0.023	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.040
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-110163768;