7-102637632-A-C

Variant names:

• chr7-102637632-A-C
• rs1216931684
• NM_001114403.3:c.685T>G

Variant summary

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

The NM_001114403.3(UPK3BL1):​c.685T>G​(p.Phe229Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 9)
  • Exomes 𝑓: 0.000039 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3BL1 NM_001114403.3 missense, splice_region
• Scores: Splicing: ADA: 0.001783
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• 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=0.05061668).

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.685T>G	p.Phe229Val	missense splice_region	Exon 6 of 6	NP_001107875.1	B0FP48
	POLR2J2-UPK3BL1	NR_173352.1		n.1037T>G		splice_region non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3BL1	ENST00000340457.8	TSL:1 MANE Select	c.685T>G	p.Phe229Val	missense splice_region	Exon 6 of 6	ENSP00000342938.8	B0FP48
	POLR2J2-UPK3BL1	ENST00000476151.5	TSL:1	n.*627T>G		splice_region non_coding_transcript_exon	Exon 9 of 9	ENSP00000418603.1
	POLR2J2-UPK3BL1	ENST00000476151.5	TSL:1	n.*627T>G		3_prime_UTR	Exon 9 of 9	ENSP00000418603.1

Frequencies

GnomAD3 genomes AF: 0.000175 AC: 13 AN: 74386 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.000382

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00114

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000145 AC: 6 AN: 41286 AF XY: 0.0000474

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000789

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: 0.0000387 AC: 15 AN: 387538 Hom.: 0 Cov.: 0 AF XY: 0.0000294 AC XY: 6 AN XY: 203836

⚠️ 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: 11536

American (AMR) AF: 0.00 AC: 0 AN: 15834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11620

East Asian (EAS) AF: 0.000363 AC: 10 AN: 27562

South Asian (SAS) AF: 0.0000721 AC: 3 AN: 41634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 230310

Other (OTH) AF: 0.0000892 AC: 2 AN: 22418

⚠️ 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: 0.000175 AC: 13 AN: 74366 Hom.: 0 Cov.: 9 AF XY: 0.000206 AC XY: 7 AN XY: 33918

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

African (AFR) AF: 0.000381 AC: 9 AN: 23600

American (AMR) AF: 0.00 AC: 0 AN: 6874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1922

East Asian (EAS) AF: 0.00114 AC: 4 AN: 3498

South Asian (SAS) AF: 0.00 AC: 0 AN: 2148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31926

Other (OTH) AF: 0.00 AC: 0 AN: 1002

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000579727), 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	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.026
Sift	Benign	0.28	T
Sift4G	Benign	0.45	T
Vest4		0.095
MutPred		0.21		Gain of disorder (P = 0.1845)
MVP		0.081
ClinPred		0.034	T
GERP RS		1.8
Varity_R		0.14
gMVP		0.20
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0018
dbscSNV1_RF	Benign	0.10
SpliceAI score (max)		0.19		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: rs1216931684; hg19: chr7-102278079;