7-102638754-C-T

Variant names:

• chr7-102638754-C-T
• rs1234025624
• NM_001114403.3:c.643G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001114403.3(UPK3BL1):​c.643G>A​(p.Val215Ile) 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 0.000034 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3BL1 NM_001114403.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.35
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09140411).

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.643G>A	p.Val215Ile	missense	Exon 5 of 6	NP_001107875.1	B0FP48
	POLR2J2-UPK3BL1	NR_173352.1		n.995G>A		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3BL1	ENST00000340457.8	TSL:1 MANE Select	c.643G>A	p.Val215Ile	missense	Exon 5 of 6	ENSP00000342938.8	B0FP48
	POLR2J2-UPK3BL1	ENST00000476151.5	TSL:1	n.*585G>A		non_coding_transcript_exon	Exon 8 of 9	ENSP00000418603.1
	ENSG00000205236	ENST00000519541.1	TSL:2	n.643G>A		non_coding_transcript_exon	Exon 5 of 26	ENSP00000429397.1	A0A286YEE6

Frequencies

GnomAD3 genomes AF: 0.0000337 AC: 5 AN: 148368 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000981

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000344 AC: 2 AN: 58072 AF XY: 0.0000678

Gnomad AFR exome AF: 0.000182

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000128

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000190 AC: 19 AN: 1002264 Hom.: 0 Cov.: 15 AF XY: 0.0000221 AC XY: 11 AN XY: 496752

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

African (AFR) AF: 0.0000397 AC: 1 AN: 25188

American (AMR) AF: 0.00 AC: 0 AN: 22302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17430

East Asian (EAS) AF: 0.0000298 AC: 1 AN: 33532

South Asian (SAS) AF: 0.00 AC: 0 AN: 58432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3032

European-Non Finnish (NFE) AF: 0.0000222 AC: 17 AN: 766194

Other (OTH) AF: 0.00 AC: 0 AN: 44418

⚠️ 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: 0.0000337 AC: 5 AN: 148368 Hom.: 0 Cov.: 25 AF XY: 0.0000554 AC XY: 4 AN XY: 72200

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

African (AFR) AF: 0.0000981 AC: 4 AN: 40758

American (AMR) AF: 0.00 AC: 0 AN: 14766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 4954

South Asian (SAS) AF: 0.00 AC: 0 AN: 4538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66550

Other (OTH) AF: 0.00 AC: 0 AN: 2030

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000423502), 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	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.26
DANN	Benign	0.89
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0024	N
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-1.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	0.42	T
Vest4		0.17
MutPred		0.39		Gain of catalytic residue at L220 (P = 0.0394)
MVP		0.014
ClinPred		0.029	T
GERP RS		-3.4
Varity_R		0.017
gMVP		0.15
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: rs1234025624; hg19: chr7-102279201;