19-17251652-C-T

Variant names:

• chr19-17251652-C-T
• ENST00000594059.1:c.-153G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000594059.1(ENSG00000269095):​c.-153G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ENSG00000269095 ENST00000594059.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.324
• Publications: 0 publications found

Genes affected

ENSG00000269095 (HGNC:):

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05068329).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594059.1. 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
	USHBP1	NM_031941.4	MANE Select	c.1852G>A	p.Val618Met	missense	Exon 12 of 13	NP_114147.2
	USHBP1	NM_001321417.2		c.1852G>A	p.Val618Met	missense	Exon 12 of 13	NP_001308346.1	Q8N6Y0-1
	USHBP1	NM_001297703.2		c.1660G>A	p.Val554Met	missense	Exon 11 of 12	NP_001284632.1	G8JLM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000269095	ENST00000594059.1	TSL:4	c.-153G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	ENSP00000473056.1	M0R384
	USHBP1	ENST00000252597.8	TSL:1 MANE Select	c.1852G>A	p.Val618Met	missense	Exon 12 of 13	ENSP00000252597.2	Q8N6Y0-1
	ENSG00000269095	ENST00000594059.1	TSL:4	c.-153G>A		5_prime_UTR	Exon 3 of 5	ENSP00000473056.1	M0R384

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

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	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.5
DANN	Benign	0.53
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.32
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.024
Sift	Benign	0.30	T
Sift4G	Benign	0.35	T
Polyphen		0.028	B
Vest4		0.16
MutPred		0.24		Gain of MoRF binding (P = 0.1321)
MVP		0.067
MPC		0.15
ClinPred		0.035	T
GERP RS		-5.5
Varity_R		0.034
gMVP		0.085
Mutation Taster		=99/1	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

hg19: chr19-17362461;