7-102638756-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001114403.3(UPK3BL1):​c.641C>T​(p.Ala214Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 25)
Exomes 𝑓: 0.000015 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

UPK3BL1
NM_001114403.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.808
Variant links:
Genes affected
UPK3BL1 (HGNC:37278): (uroplakin 3B like 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18570188).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UPK3BL1NM_001114403.3 linkc.641C>T p.Ala214Val missense_variant Exon 5 of 6 ENST00000340457.8 NP_001107875.1 B0FP48E5RIL1
POLR2J2-UPK3BL1NR_173352.1 linkn.993C>T non_coding_transcript_exon_variant Exon 8 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UPK3BL1ENST00000340457.8 linkc.641C>T p.Ala214Val missense_variant Exon 5 of 6 1 NM_001114403.3 ENSP00000342938.8 B0FP48
ENSG00000267645ENST00000476151.5 linkn.*583C>T non_coding_transcript_exon_variant Exon 8 of 9 1 ENSP00000418603.1
ENSG00000205236ENST00000519541.1 linkn.641C>T non_coding_transcript_exon_variant Exon 5 of 26 2 ENSP00000429397.1 A0A286YEE6
ENSG00000267645ENST00000476151.5 linkn.*583C>T 3_prime_UTR_variant Exon 8 of 9 1 ENSP00000418603.1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
4
AN:
148528
Hom.:
0
Cov.:
25
FAILED QC
Gnomad AFR
AF:
0.0000245
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000201
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000300
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000148
AC:
15
AN:
1010940
Hom.:
0
Cov.:
16
AF XY:
0.0000200
AC XY:
10
AN XY:
500660
show subpopulations
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:
0.0000341
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000155
Gnomad4 OTH exome
AF:
0.0000224
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000269
AC:
4
AN:
148528
Hom.:
0
Cov.:
25
AF XY:
0.0000277
AC XY:
2
AN XY:
72294
show subpopulations
Gnomad4 AFR
AF:
0.0000245
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000201
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000300
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000306
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.641C>T (p.A214V) alteration is located in exon 5 (coding exon 5) of the UPK3BL gene. This alteration results from a C to T substitution at nucleotide position 641, causing the alanine (A) at amino acid position 214 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.073
T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.061
N
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.080
Sift
Benign
0.11
T
Sift4G
Uncertain
0.012
D
Vest4
0.24
MutPred
0.39
Loss of helix (P = 0.079);
MVP
0.061
ClinPred
0.34
T
GERP RS
-0.37
Varity_R
0.047
gMVP
0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1176860698; hg19: chr7-102279203; API