16-19872317-C-CGAT

Position:

• chr16-19872317-C-CGAT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_016235.3(GPRC5B):​c.526_528dupATC​(p.Ile176dup) variant causes a conservative inframe insertion 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPRC5B NM_016235.3 conservative_inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.205

Genes affected

GPRC5B (HGNC:13308): (G protein-coupled receptor class C group 5 member B) This gene encodes a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The encoded protein may modulate insulin secretion and increased protein expression is associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_016235.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 16-19872317-C-CGAT is Pathogenic according to our data. Variant chr16-19872317-C-CGAT is described in ClinVar as [Pathogenic]. Clinvar id is 2573133.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5B	NM_016235.3	c.526_528dupATC	p.Ile176dup	conservative_inframe_insertion	2/4	ENST00000300571.7	NP_057319.1
GPRC5B	NM_001304771.1	c.919_921dupATC	p.Ile307dup	conservative_inframe_insertion	2/4		NP_001291700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5B	ENST00000300571.7	c.526_528dupATC	p.Ile176dup	conservative_inframe_insertion	2/4	1	NM_016235.3	ENSP00000300571.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr16-19883639;