2-3695718-T-A

Position:

• chr2-3695718-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018436.4(ALLC):​c.513T>A​(p.Asp171Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALLC NM_018436.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001764
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.466

Genes affected

ALLC (HGNC:17377): (allantoicase) Allantoicase (EC 3.5.3.4) participates in the uric acid degradation pathway. Its enzymatic activity, like that of urate oxidase (MIM 191540), was lost during vertebrate evolution.[supplied by OMIM, Nov 2008]

ALLC (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALLC	NM_018436.4	c.513T>A	p.Asp171Glu	missense_variant, splice_region_variant	8/12	ENST00000252505.4	NP_060906.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALLC	ENST00000252505.4	c.513T>A	p.Asp171Glu	missense_variant, splice_region_variant	8/12	1	NM_018436.4	ENSP00000252505.3
ALLC	ENST00000471711.1	n.177T>A		splice_region_variant, non_coding_transcript_exon_variant	2/6	3
ALLC	ENST00000476389.5	n.1098T>A		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 23, 2021

The c.513T>A (p.D171E) alteration is located in exon 8 (coding exon 7) of the ALLC gene. This alteration results from a T to A substitution at nucleotide position 513, causing the aspartic acid (D) at amino acid position 171 to be replaced by a glutamic acid (E). 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	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.19
Eigen_PC	Benign	-0.015
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0036	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.022	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.88
MVP		0.048
MPC		0.36
ClinPred		1.0	D
GERP RS		0.30
Varity_R		0.79
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.076
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.48		Position offset: 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: chr2-3743308;