11-3640238-A-G

Position:

• chr11-3640238-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_053017.5(ART5):​c.191T>C​(p.Leu64Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ART5 NM_053017.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

ART5 (HGNC:24049): (ADP-ribosyltransferase 5) The protein encoded by this gene belongs to the ARG-specific ADP-ribosyltransferase family. Proteins in this family regulate the function of target proteins by attaching ADP-ribose to specific amino acid residues in their target proteins. The mouse homolog lacks a glycosylphosphatidylinositol-anchor signal sequence and is predicted to be a secretory enzyme. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ART5 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ART5	NM_053017.5	c.191T>C	p.Leu64Pro	missense_variant	2/4	ENST00000397068.8	NP_443750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ART5	ENST00000397068.8	c.191T>C	p.Leu64Pro	missense_variant	2/4	1	NM_053017.5	ENSP00000380258.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 92

GnomAD4 genome Cov.: 34

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

Feb 10, 2022

The c.191T>C (p.L64P) alteration is located in exon 2 (coding exon 2) of the ART5 gene. This alteration results from a T to C substitution at nucleotide position 191, causing the leucine (L) at amino acid position 64 to be replaced by a proline (P). 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	0.69
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.78	.;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.96	D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.4	M;M;M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Uncertain	0.42
Sift	Benign	0.060	T;D;T;D
Sift4G	Uncertain	0.0030	D;D;D;.
Polyphen		1.0	D;D;D;.
Vest4		0.89
MutPred		0.90		Loss of stability (P = 0.0071);Loss of stability (P = 0.0071);Loss of stability (P = 0.0071);.;
MVP		0.30
MPC		0.36
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.93
gMVP		0.93

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: chr11-3661468;