chr7-102638727-G-A

Variant names:

• chr7-102638727-G-A
• rs1306550907
• NM_001114403.3:c.670C>T

Variant summary

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

The NM_001114403.3(UPK3BL1):​c.670C>T​(p.Leu224Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3BL1 NM_001114403.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.198
• 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=0.15547988).

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.670C>T	p.Leu224Phe	missense	Exon 5 of 6	NP_001107875.1	B0FP48
	POLR2J2-UPK3BL1	NR_173352.1		n.1022C>T		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.670C>T	p.Leu224Phe	missense	Exon 5 of 6	ENSP00000342938.8	B0FP48
	POLR2J2-UPK3BL1	ENST00000476151.5	TSL:1	n.*612C>T		non_coding_transcript_exon	Exon 8 of 9	ENSP00000418603.1
	ENSG00000205236	ENST00000519541.1	TSL:2	n.670C>T		non_coding_transcript_exon	Exon 5 of 26	ENSP00000429397.1	A0A286YEE6

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 16 AN: 146700 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000138

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000173 AC: 1 AN: 57680 AF XY: 0.00

Gnomad AFR exome AF: 0.000184

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 0.0000114 AC: 11 AN: 967610 Hom.: 0 Cov.: 14 AF XY: 0.0000125 AC XY: 6 AN XY: 480896

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

African (AFR) AF: 0.000408 AC: 10 AN: 24522

American (AMR) AF: 0.00 AC: 0 AN: 23164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17336

East Asian (EAS) AF: 0.00 AC: 0 AN: 33326

South Asian (SAS) AF: 0.00 AC: 0 AN: 58082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2970

European-Non Finnish (NFE) AF: 0.00000136 AC: 1 AN: 734346

Other (OTH) AF: 0.00 AC: 0 AN: 43228

⚠️ 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: 0.000109 AC: 16 AN: 146814 Hom.: 0 Cov.: 25 AF XY: 0.000126 AC XY: 9 AN XY: 71386

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

African (AFR) AF: 0.000347 AC: 14 AN: 40334

American (AMR) AF: 0.000137 AC: 2 AN: 14546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4902

South Asian (SAS) AF: 0.00 AC: 0 AN: 4438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66018

Other (OTH) AF: 0.00 AC: 0 AN: 2014

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.11	N
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.20
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.040
Sift	Benign	0.17	T
Sift4G	Uncertain	0.032	D
Vest4		0.35
MutPred		0.34		Loss of helix (P = 0.2271)
MVP		0.061
ClinPred		0.19	T
GERP RS		-0.20
Varity_R		0.098
gMVP		0.30
Mutation Taster		=100/0	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: rs1306550907; hg19: chr7-102279174;