chr6-116792738-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_148963.4(GPRC6A):ā€‹c.2185A>Gā€‹(p.Thr729Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.000037 ( 0 hom. )

Consequence

GPRC6A
NM_148963.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.39
Variant links:
Genes affected
GPRC6A (HGNC:18510): (G protein-coupled receptor class C group 6 member A) Members of family C of the G protein-coupled receptor (GPCR) superfamily, such as GPRC6A, are characterized by an evolutionarily conserved amino acid-sensing motif linked to an intramembranous 7-transmembrane loop region. Several members of GPCR family C, including GPRC6A, also have a long N-terminal domain (summary by Pi et al., 2005 [PubMed 16199532]).[supplied by OMIM, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.01935935).
BP6
Variant 6-116792738-T-C is Benign according to our data. Variant chr6-116792738-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3101997.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPRC6ANM_148963.4 linkuse as main transcriptc.2185A>G p.Thr729Ala missense_variant 6/6 ENST00000310357.8 NP_683766.2
GPRC6ANM_001286355.1 linkuse as main transcriptc.1972A>G p.Thr658Ala missense_variant 5/5 NP_001273284.1
GPRC6ANM_001286354.1 linkuse as main transcriptc.1660A>G p.Thr554Ala missense_variant 6/6 NP_001273283.1
GPRC6AXM_017010475.2 linkuse as main transcriptc.2044A>G p.Thr682Ala missense_variant 7/7 XP_016865964.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPRC6AENST00000310357.8 linkuse as main transcriptc.2185A>G p.Thr729Ala missense_variant 6/61 NM_148963.4 ENSP00000309493 P1Q5T6X5-1
GPRC6AENST00000368549.7 linkuse as main transcriptc.1972A>G p.Thr658Ala missense_variant 5/51 ENSP00000357537 Q5T6X5-3
GPRC6AENST00000530250.1 linkuse as main transcriptc.1660A>G p.Thr554Ala missense_variant 6/61 ENSP00000433465 Q5T6X5-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152134
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000771
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000718
AC:
18
AN:
250564
Hom.:
0
AF XY:
0.0000886
AC XY:
12
AN XY:
135372
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000979
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461538
Hom.:
0
Cov.:
36
AF XY:
0.0000358
AC XY:
26
AN XY:
727020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00128
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152252
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000773
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.000124
AC:
15

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 05, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
1.8
DANN
Benign
0.38
DEOGEN2
Benign
0.084
T;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.41
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.019
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.20
N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.57
N;N;N
REVEL
Benign
0.20
Sift
Benign
0.71
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.016
MVP
0.35
MPC
0.042
ClinPred
0.0083
T
GERP RS
-7.9
Varity_R
0.025
gMVP
0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200330140; hg19: chr6-117113901; API