chr19-3148657-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002068.4(GNA15):c.212C>T(p.Ser71Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,438,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
GNA15
NM_002068.4 missense
NM_002068.4 missense
Scores
9
7
Clinical Significance
Conservation
PhyloP100: 4.05
Genes affected
GNA15 (HGNC:4383): (G protein subunit alpha 15) Enables G protein-coupled receptor binding activity. Involved in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to be located in plasma membrane. Predicted to be part of heterotrimeric G-protein complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNA15 | NM_002068.4 | c.212C>T | p.Ser71Leu | missense_variant | 2/7 | ENST00000262958.4 | |
GNA15-DT | NR_110670.1 | n.1292G>A | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNA15 | ENST00000262958.4 | c.212C>T | p.Ser71Leu | missense_variant | 2/7 | 1 | NM_002068.4 | P1 | |
GNA15-DT | ENST00000587587.1 | n.1292G>A | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
GNA15 | ENST00000592455.1 | c.*242C>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000278 AC: 4AN: 1438828Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1AN XY: 713610
GnomAD4 exome
AF:
AC:
4
AN:
1438828
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
713610
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Bravo
AF:
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 | Oct 05, 2023 | The c.212C>T (p.S71L) alteration is located in exon 2 (coding exon 2) of the GNA15 gene. This alteration results from a C to T substitution at nucleotide position 212, causing the serine (S) at amino acid position 71 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Vest4
MutPred
Gain of stability (P = 0.0174);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at