NM_001075.6:c.407T>G

Variant names:

• chr4-68816426-T-G
• NM_001075.6:c.407T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001075.6(UGT2B10):​c.407T>G​(p.Met136Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.71

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B10	NM_001075.6	c.407T>G	p.Met136Arg	missense_variant	Exon 1 of 6	ENST00000265403.12	NP_001066.1
UGT2B10	NM_001144767.3	c.407T>G	p.Met136Arg	missense_variant	Exon 1 of 6		NP_001138239.1
UGT2B10	XM_017008585.3	c.407T>G	p.Met136Arg	missense_variant	Exon 1 of 6		XP_016864074.1
UGT2B10	NM_001290091.2	c.-27+254T>G		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.407T>G	p.Met136Arg	missense_variant	Exon 1 of 6	1	NM_001075.6	ENSP00000265403.7
UGT2B10	ENST00000458688.2	c.407T>G	p.Met136Arg	missense_variant	Exon 1 of 6	2		ENSP00000413420.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460920 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726780

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	0.094
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.7	H;H
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.56
MutPred		0.76		Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);
MVP		0.52
MPC		0.042
ClinPred		0.94	D
GERP RS		2.6
Varity_R		0.55
gMVP		0.60

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: chr4-69682144;