7-102639134-C-T

Variant names:

• chr7-102639134-C-T
• rs201129776
• NM_001114403.3:c.551G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001114403.3(UPK3BL1):​c.551G>A​(p.Arg184His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 148,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3BL1 NM_001114403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013486475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK3BL1	NM_001114403.3	c.551G>A	p.Arg184His	missense_variant	Exon 4 of 6	ENST00000340457.8	NP_001107875.1
POLR2J2-UPK3BL1	NR_173352.1	n.903G>A		non_coding_transcript_exon_variant	Exon 7 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPK3BL1	ENST00000340457.8	c.551G>A	p.Arg184His	missense_variant	Exon 4 of 6	1	NM_001114403.3	ENSP00000342938.8
ENSG00000267645	ENST00000476151.5	n.*493G>A		non_coding_transcript_exon_variant	Exon 7 of 9	1		ENSP00000418603.1
ENSG00000205236	ENST00000519541.1	n.551G>A		non_coding_transcript_exon_variant	Exon 4 of 26	2		ENSP00000429397.1
ENSG00000267645	ENST00000476151.5	n.*493G>A		3_prime_UTR_variant	Exon 7 of 9	1		ENSP00000418603.1

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 689 AN: 147960 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00297

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00198

Gnomad SAS AF: 0.00147

Gnomad FIN AF: 0.00730

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000517

Gnomad OTH AF: 0.00538

GnomAD3 exomes AF: 0.00203 AC: 312 AN: 153424 Hom.: 0 AF XY: 0.00174 AC XY: 142 AN XY: 81418

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.00184

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00158

Gnomad SAS exome AF: 0.000398

Gnomad FIN exome AF: 0.00792

Gnomad NFE exome AF: 0.000454

Gnomad OTH exome AF: 0.00184

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000789 AC: 1095 AN: 1388072 Hom.: 3 Cov.: 65 AF XY: 0.000718 AC XY: 492 AN XY: 684956

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.00173

Gnomad4 ASJ exome AF: 0.0000399

Gnomad4 EAS exome AF: 0.00179

Gnomad4 SAS exome AF: 0.000470

Gnomad4 FIN exome AF: 0.00703

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00469 AC: 694 AN: 148062 Hom.: 0 Cov.: 33 AF XY: 0.00489 AC XY: 354 AN XY: 72432

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00290

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00199

Gnomad4 SAS AF: 0.00147

Gnomad4 FIN AF: 0.00730

Gnomad4 NFE AF: 0.000517

Gnomad4 OTH AF: 0.00580

Alfa AF: 0.00207 Hom.: 0

ExAC AF: 0.00401 AC: 130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.0040
DANN	Benign	0.84
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0011	N
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.94	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.079
Sift	Benign	0.54	T
Sift4G	Benign	0.54	T
Vest4		0.046
MVP		0.014
ClinPred		0.0067	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.018
gMVP		0.25

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

Other links and lift over

dbSNP: rs201129776; hg19: chr7-102279581; COSMIC: COSV61014918;