3-120167552-CT-C

Variant names:

• chr3-120167552-CT-C
• NM_153002.3:c.1924delA

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_153002.3(GPR156):​c.1924delA​(p.Ser642AlafsTer162) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR156 NM_153002.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.690

Genes affected

GPR156 (HGNC:20844): (G protein-coupled receptor 156) G protein-coupled receptors (GPCRs) are a large superfamily of cell surface receptors characterized by 7 helical transmembrane domains, together with N-terminal extracellular and C-terminal intracellular domains.[supplied by OMIM, Mar 2008]

LOC105374065 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.213 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-120167552-CT-C is Pathogenic according to our data. Variant chr3-120167552-CT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3064875.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR156	NM_153002.3	c.1924delA	p.Ser642AlafsTer162	frameshift_variant	Exon 10 of 10	ENST00000464295.6	NP_694547.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR156	ENST00000464295.6	c.1924delA	p.Ser642AlafsTer162	frameshift_variant	Exon 10 of 10	5	NM_153002.3	ENSP00000417261.1
GPR156	ENST00000461057.1	c.1912delA	p.Ser638AlafsTer162	frameshift_variant	Exon 9 of 9	1		ENSP00000418758.1
GPR156	ENST00000495912.5	n.*987delA		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000417191.1
GPR156	ENST00000495912.5	n.*987delA		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000417191.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hearing loss, autosomal recessive 121 Pathogenic:1

Mar 25, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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: chr3-119886399;