7-102639141-C-T

Variant names:

• chr7-102639141-C-T
• rs1158813055
• NM_001114403.3:c.544G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001114403.3(UPK3BL1):​c.544G>A​(p.Asp182Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3BL1 NM_001114403.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.324
• Publications: 0 publications found

Genes affected

UPK3BL1 (HGNC:37278): (uroplakin 3B like 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

POLR2J2-UPK3BL1 (HGNC:58364):

ENSG00000205236 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06008345).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114403.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3BL1	NM_001114403.3	MANE Select	c.544G>A	p.Asp182Asn	missense	Exon 4 of 6	NP_001107875.1	B0FP48
	POLR2J2-UPK3BL1	NR_173352.1		n.896G>A		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3BL1	ENST00000340457.8	TSL:1 MANE Select	c.544G>A	p.Asp182Asn	missense	Exon 4 of 6	ENSP00000342938.8	B0FP48
	POLR2J2-UPK3BL1	ENST00000476151.5	TSL:1	n.*486G>A		non_coding_transcript_exon	Exon 7 of 9	ENSP00000418603.1
	ENSG00000205236	ENST00000519541.1	TSL:2	n.544G>A		non_coding_transcript_exon	Exon 4 of 26	ENSP00000429397.1	A0A286YEE6

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152008 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000452 AC: 7 AN: 154832 AF XY: 0.0000610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000459

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000335

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000438 AC: 61 AN: 1393470 Hom.: 0 Cov.: 68 AF XY: 0.0000538 AC XY: 37 AN XY: 687496

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31580

American (AMR) AF: 0.0000562 AC: 2 AN: 35590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25080

East Asian (EAS) AF: 0.000168 AC: 6 AN: 35680

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.0000438 AC: 47 AN: 1073684

Other (OTH) AF: 0.0000692 AC: 4 AN: 57840

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000526 AC: 8 AN: 152126 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74382

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67938

Other (OTH) AF: 0.00 AC: 0 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0059	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.32
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.082
Sift	Benign	0.22	T
Sift4G	Benign	0.25	T
Vest4		0.039
MutPred		0.34		Gain of MoRF binding (P = 0.0737)
MVP		0.014
ClinPred		0.032	T
GERP RS		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.20
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1158813055; hg19: chr7-102279588;