Variant 16-19872185-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016235.3(GPRC5B):c.661A>C(p.Thr221Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPRC5B
NM_016235.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Variant links:

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]

GPRC5B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31279558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5B	NM_016235.3 linkuse as main transcript	c.661A>C	p.Thr221Pro	missense_variant	2/4	ENST00000300571.7	NP_057319.1	Q9NZH0-1A0A024QYX2
GPRC5B	NM_001304771.1 linkuse as main transcript	c.1054A>C	p.Thr352Pro	missense_variant	2/4		NP_001291700.1	B7Z831

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPRC5B	ENST00000300571.7 linkuse as main transcript	c.661A>C	p.Thr221Pro	missense_variant	2/4	1	NM_016235.3	ENSP00000300571.2	Q9NZH0-1
GPRC5B	ENST00000535671.5 linkuse as main transcript	c.661A>C	p.Thr221Pro	missense_variant	1/3	1		ENSP00000442858.1	Q9NZH0-2
GPRC5B	ENST00000569479.5 linkuse as main transcript	c.661A>C	p.Thr221Pro	missense_variant	2/4	5		ENSP00000454727.1	Q9NZH0-1
GPRC5B	ENST00000569847.1 linkuse as main transcript	c.661A>C	p.Thr221Pro	missense_variant	2/4	2		ENSP00000457283.1	Q9NZH0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.661A>C (p.T221P) alteration is located in exon 2 (coding exon 1) of the GPRC5B gene. This alteration results from a A to C substitution at nucleotide position 661, causing the threonine (T) at amino acid position 221 to be replaced by a proline (P). 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

0.15

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.83

D;.;D;D

Eigen

Benign

0.14

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

.;T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M;M

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.6

D;D;D;D

REVEL

Benign

0.27

Sift

Benign

0.074

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.97

D;.;D;D

Vest4

0.51

MVP

0.20

MPC

1.3

ClinPred

0.90

GERP RS

1.7

Varity_R

0.38

gMVP

0.93

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over