4-114623245-C-A

Position:

• chr4-114623245-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000310836.11(UGT8):​c.365C>A​(p.Ala122Asp) 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. 16/21 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: UGT8 ENST00000310836.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77

Genes affected

UGT8 (HGNC:12555): (UDP glycosyltransferase 8) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. It catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central and peripheral nervous systems. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1364542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT8	NM_001128174.3	c.365C>A	p.Ala122Asp	missense_variant	2/6	ENST00000310836.11	NP_001121646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT8	ENST00000310836.11	c.365C>A	p.Ala122Asp	missense_variant	2/6	1	NM_001128174.3	ENSP00000311648	P1
UGT8	ENST00000394511.3	c.365C>A	p.Ala122Asp	missense_variant	1/5	1		ENSP00000378019	P1
UGT8	ENST00000507710.1	c.365C>A	p.Ala122Asp	missense_variant	3/3	3		ENSP00000421446

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Apr 04, 2023

The c.365C>A (p.A122D) alteration is located in exon 2 (coding exon 1) of the UGT8 gene. This alteration results from a C to A substitution at nucleotide position 365, causing the alanine (A) at amino acid position 122 to be replaced by an aspartic acid (D). 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	0.088
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.22	T;T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.59	.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.45	N;.;N
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.22	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.18
MutPred		0.61		Gain of disorder (P = 0.1171);Gain of disorder (P = 0.1171);Gain of disorder (P = 0.1171);
MVP		0.61
MPC		0.44
ClinPred		0.42	T
GERP RS		2.4
Varity_R		0.27
gMVP		0.76

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: chr4-115544401;