7-102638822-C-T

Variant names:

• chr7-102638822-C-T
• rs1187093163
• NM_001114403.3:c.575G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001114403.3(UPK3BL1):​c.575G>A​(p.Arg192Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0010 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3BL1 NM_001114403.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

Genes affected

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

ENSG00000267645 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03216964).
• BP6: Variant 7-102638822-C-T is Benign according to our data. Variant chr7-102638822-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3186831.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK3BL1	NM_001114403.3	c.575G>A	p.Arg192Gln	missense_variant	Exon 5 of 6	ENST00000340457.8	NP_001107875.1
POLR2J2-UPK3BL1	NR_173352.1	n.927G>A		non_coding_transcript_exon_variant	Exon 8 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPK3BL1	ENST00000340457.8	c.575G>A	p.Arg192Gln	missense_variant	Exon 5 of 6	1	NM_001114403.3	ENSP00000342938.8
ENSG00000267645	ENST00000476151.5	n.*517G>A		non_coding_transcript_exon_variant	Exon 8 of 9	1		ENSP00000418603.1
ENSG00000205236	ENST00000519541.1	n.575G>A		non_coding_transcript_exon_variant	Exon 5 of 26	2		ENSP00000429397.1
ENSG00000267645	ENST00000476151.5	n.*517G>A		3_prime_UTR_variant	Exon 8 of 9	1		ENSP00000418603.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 156 AN: 148918 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

Gnomad ASJ AF: 0.00147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00164

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.000975

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00235 AC: 2815 AN: 1200322 Hom.: 0 Cov.: 25 AF XY: 0.00229 AC XY: 1337 AN XY: 583914

Gnomad4 AFR exome AF: 0.000400

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.000117

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.00251

Gnomad4 NFE exome AF: 0.00261

Gnomad4 OTH exome AF: 0.00234

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00104 AC: 155 AN: 149036 Hom.: 0 Cov.: 26 AF XY: 0.000921 AC XY: 67 AN XY: 72716

Gnomad4 AFR AF: 0.000243

Gnomad4 AMR AF: 0.000201

Gnomad4 ASJ AF: 0.00147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00164

Gnomad4 NFE AF: 0.00177

Gnomad4 OTH AF: 0.000964

Alfa AF: 0.00234 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 09, 2022

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	0.073
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.091
DANN	Benign	0.91
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00049	N
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.51	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.0090
Sift	Benign	0.73	T
Sift4G	Benign	0.74	T
Vest4		0.038
MutPred		0.24		Gain of disorder (P = 0.0954);
MVP		0.040
ClinPred		0.0073	T
GERP RS		-3.0
Varity_R		0.025
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1187093163; hg19: chr7-102279269;