chr4-68816336-T-C

Variant names:

• chr4-68816336-T-C
• NM_001075.6:c.317T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001075.6(UGT2B10):​c.317T>C​(p.Leu106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67

Genes affected

UGT2B10 (HGNC:12544): (UDP glucuronosyltransferase family 2 member B10) Predicted to be involved in lipid metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01946327).
• BP6: Variant 4-68816336-T-C is Benign according to our data. Variant chr4-68816336-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2241371.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B10	NM_001075.6	c.317T>C	p.Leu106Ser	missense_variant	Exon 1 of 6	ENST00000265403.12	NP_001066.1
UGT2B10	NM_001144767.3	c.317T>C	p.Leu106Ser	missense_variant	Exon 1 of 6		NP_001138239.1
UGT2B10	XM_017008585.3	c.317T>C	p.Leu106Ser	missense_variant	Exon 1 of 6		XP_016864074.1
UGT2B10	NM_001290091.2	c.-27+164T>C		intron_variant	Intron 1 of 5		NP_001277020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B10	ENST00000265403.12	c.317T>C	p.Leu106Ser	missense_variant	Exon 1 of 6	1	NM_001075.6	ENSP00000265403.7
UGT2B10	ENST00000458688.2	c.317T>C	p.Leu106Ser	missense_variant	Exon 1 of 6	2		ENSP00000413420.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461104 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726860

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 04, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.012
DANN	Benign	0.49
DEOGEN2	Benign	0.0031	T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.014	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.019	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	2.4	N;N
REVEL	Benign	0.0090
Sift	Benign	0.78	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.0010	B;.
Vest4		0.083
MutPred		0.42		Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);
MVP		0.088
MPC		0.0091
ClinPred		0.081	T
GERP RS		-5.3
Varity_R		0.033
gMVP		0.11

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: chr4-69682054;