ENST00000594059.1:c.-153G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USHBP1	NM_031941.4	c.1852G>A	p.Val618Met	missense_variant	Exon 12 of 13	ENST00000252597.8	NP_114147.2
USHBP1	NM_001321417.2	c.1852G>A	p.Val618Met	missense_variant	Exon 12 of 13		NP_001308346.1
USHBP1	NM_001297703.2	c.1660G>A	p.Val554Met	missense_variant	Exon 11 of 12		NP_001284632.1
USHBP1	NR_135632.2	n.2093G>A		non_coding_transcript_exon_variant	Exon 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269095	ENST00000594059.1	c.-153G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 5	4		ENSP00000473056.1
USHBP1	ENST00000252597.8	c.1852G>A	p.Val618Met	missense_variant	Exon 12 of 13	1	NM_031941.4	ENSP00000252597.2
ENSG00000269095	ENST00000594059.1	c.-153G>A		5_prime_UTR_variant	Exon 3 of 5	4		ENSP00000473056.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1852G>A (p.V618M) alteration is located in exon 12 (coding exon 11) of the USHBP1 gene. This alteration results from a G to A substitution at nucleotide position 1852, causing the valine (V) at amino acid position 618 to be replaced by a methionine (M). 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	0.12
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;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.60	N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.024
Sift	Benign	0.30	T;T
Sift4G	Benign	0.35	T;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17362461;