NM_001114403.3:c.749C>A

Variant names:

• chr7-102637568-G-T
• rs1429218989
• NM_001114403.3:c.749C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001114403.3(UPK3BL1):​c.749C>A​(p.Thr250Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0000049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3BL1 NM_001114403.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00400
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04559478).
• BP6: Variant 7-102637568-G-T is Benign according to our data. Variant chr7-102637568-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3331161.Status of the report is criteria_provided_single_submitter, 1 stars.

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.749C>A	p.Thr250Asn	missense	Exon 6 of 6	NP_001107875.1	B0FP48
	POLR2J2-UPK3BL1	NR_173352.1		n.1101C>A		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.749C>A	p.Thr250Asn	missense	Exon 6 of 6	ENSP00000342938.8	B0FP48
	POLR2J2-UPK3BL1	ENST00000476151.5	TSL:1	n.*691C>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000418603.1
	POLR2J2-UPK3BL1	ENST00000476151.5	TSL:1	n.*691C>A		3_prime_UTR	Exon 9 of 9	ENSP00000418603.1

Frequencies

GnomAD3 genomes AF: 0.0000280 AC: 3 AN: 107304 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000932

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000112 AC: 4 AN: 35678 AF XY: 0.000163

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000546

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: 0.00000494 AC: 2 AN: 404714 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 212206

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

African (AFR) AF: 0.0000850 AC: 1 AN: 11758

American (AMR) AF: 0.00 AC: 0 AN: 15758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12102

East Asian (EAS) AF: 0.00 AC: 0 AN: 28348

South Asian (SAS) AF: 0.00 AC: 0 AN: 41262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1718

European-Non Finnish (NFE) AF: 0.00000411 AC: 1 AN: 243420

Other (OTH) AF: 0.00 AC: 0 AN: 23390

⚠️ 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: 0.0000280 AC: 3 AN: 107304 Hom.: 0 Cov.: 16 AF XY: 0.0000397 AC XY: 2 AN XY: 50334

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

African (AFR) AF: 0.0000932 AC: 3 AN: 32198

American (AMR) AF: 0.00 AC: 0 AN: 10038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2608

East Asian (EAS) AF: 0.00 AC: 0 AN: 4304

South Asian (SAS) AF: 0.00 AC: 0 AN: 3124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47204

Other (OTH) AF: 0.00 AC: 0 AN: 1404

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0183214), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000337 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.087
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.3
DANN	Benign	0.79
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0034	N
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.050	N
PhyloP100		-0.0040
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.031
Sift	Benign	0.76	T
Sift4G	Benign	0.70	T
Vest4		0.059
MutPred		0.17		Loss of glycosylation at T250 (P = 0.0336)
MVP		0.030
ClinPred		0.037	T
GERP RS		-0.62
Varity_R		0.032
gMVP		0.24
Mutation Taster		=91/9	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: rs1429218989; hg19: chr7-102278015;