chr19-17255416-C-T

Variant names:

• chr19-17255416-C-T
• NM_031941.4:c.1661G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031941.4(USHBP1):​c.1661G>A​(p.Gly554Asp) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USHBP1 NM_031941.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0100

Genes affected

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

ENSG00000269095 (HGNC:):

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=0.02842611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USHBP1	NM_031941.4	c.1661G>A	p.Gly554Asp	missense_variant	Exon 10 of 13	ENST00000252597.8	NP_114147.2
USHBP1	NM_001321417.2	c.1661G>A	p.Gly554Asp	missense_variant	Exon 10 of 13		NP_001308346.1
USHBP1	NM_001297703.2	c.1469G>A	p.Gly490Asp	missense_variant	Exon 9 of 12		NP_001284632.1
USHBP1	NR_135632.2	n.1902G>A		non_coding_transcript_exon_variant	Exon 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USHBP1	ENST00000252597.8	c.1661G>A	p.Gly554Asp	missense_variant	Exon 10 of 13	1	NM_031941.4	ENSP00000252597.2
ENSG00000269095	ENST00000594059.1	c.-344G>A		5_prime_UTR_variant	Exon 1 of 5	4		ENSP00000473056.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1661G>A (p.G554D) alteration is located in exon 10 (coding exon 9) of the USHBP1 gene. This alteration results from a G to A substitution at nucleotide position 1661, causing the glycine (G) at amino acid position 554 to be replaced by an aspartic acid (D). 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	0.075
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.69
DANN	Benign	0.58
DEOGEN2	Benign	0.0055	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.028	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.44	N;N
REVEL	Benign	0.028
Sift	Benign	0.72	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0	B;.
Vest4		0.12
MutPred		0.085		Gain of solvent accessibility (P = 0.0638);.;
MVP		0.055
MPC		0.19
ClinPred		0.032	T
GERP RS		-5.8
Varity_R		0.028
gMVP		0.15

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: chr19-17366225;