chr13-46791376-C-G

Position:

• chr13-46791376-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001984.2(ESD):​c.38G>C​(p.Gly13Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ESD NM_001984.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59

Genes affected

ESD (HGNC:3465): (esterase D) This gene encodes a serine hydrolase that belongs to the esterase D family. The encoded enzyme is active toward numerous substrates including O-acetylated sialic acids, and it may be involved in the recycling of sialic acids. This gene is used as a genetic marker for retinoblastoma and Wilson's disease. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35839716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESD	NM_001984.2	c.38G>C	p.Gly13Ala	missense_variant	3/10	ENST00000378720.8
ESD	XM_005266278.4	c.38G>C	p.Gly13Ala	missense_variant	3/10
ESD	XM_011534954.2	c.38G>C	p.Gly13Ala	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESD	ENST00000378720.8	c.38G>C	p.Gly13Ala	missense_variant	3/10	1	NM_001984.2	P1
ESD	ENST00000471867.3	c.38G>C	p.Gly13Ala	missense_variant	3/9	2
ESD	ENST00000378697.5	c.-115G>C		5_prime_UTR_variant	3/11	5
ESD	ENST00000495654.1	n.87G>C		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460848 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726738

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: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000378

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

Jun 22, 2024

The c.38G>C (p.G13A) alteration is located in exon 3 (coding exon 1) of the ESD gene. This alteration results from a G to C substitution at nucleotide position 38, causing the glycine (G) at amino acid position 13 to be replaced by an alanine (A). 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	0.20
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.3	M
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.19	B
Vest4		0.37
MutPred		0.53		Gain of catalytic residue at G13 (P = 0.0014);
MVP		0.65
MPC		0.17
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
gMVP		0.74

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: rs772595780; hg19: chr13-47365511;