rs148037291

Variant names:

• chr19-17251595-A-C
• rs148037291
• NM_031941.4:c.1909T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-17251595-A-C
• chr19-17251595-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031941.4(USHBP1):​c.1909T>G​(p.Cys637Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C637R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: USHBP1 NM_031941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USHBP1	NM_031941.4	c.1909T>G	p.Cys637Gly	missense_variant	Exon 12 of 13	ENST00000252597.8	NP_114147.2
USHBP1	NM_001321417.2	c.1909T>G	p.Cys637Gly	missense_variant	Exon 12 of 13		NP_001308346.1
USHBP1	NM_001297703.2	c.1717T>G	p.Cys573Gly	missense_variant	Exon 11 of 12		NP_001284632.1
USHBP1	NR_135632.2	n.2150T>G		non_coding_transcript_exon_variant	Exon 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USHBP1	ENST00000252597.8	c.1909T>G	p.Cys637Gly	missense_variant	Exon 12 of 13	1	NM_031941.4	ENSP00000252597.2
ENSG00000269095	ENST00000594059.1	c.-96T>G		5_prime_UTR_variant	Exon 3 of 5	4		ENSP00000473056.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461744 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Benign	0.83
DEOGEN2	Benign	0.065	T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		4.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.14
Sift	Benign	0.46	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.69	P;.
Vest4		0.59
MutPred		0.34		Loss of stability (P = 0.0038);.;
MVP		0.25
MPC		0.44
ClinPred		0.78	D
GERP RS		4.4
Varity_R		0.28
gMVP		0.068
Mutation Taster		=97/3	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: rs148037291; hg19: chr19-17362404;