rs71651682

Variant names:

• chr15-26772759-C-A
• NM_000814.6:c.94G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-26772759-C-A
• chr15-26772759-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001278631.2(GABRB3):​c.-258G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,980 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GABRB3 NM_001278631.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

ACMG classification

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 rank	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.94G>T	p.Gly32Trp	missense_variant	Exon 2 of 9	ENST00000311550.10	NP_000805.1
GABRB3	NM_001278631.2	c.-258G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 10		NP_001265560.1
GABRB3	NM_021912.5	c.94G>T	p.Gly32Trp	missense_variant	Exon 2 of 9		NP_068712.1
GABRB3	NM_001278631.2	c.-258G>T		5_prime_UTR_variant	Exon 2 of 10		NP_001265560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.94G>T	p.Gly32Trp	missense_variant	Exon 2 of 9	1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388980 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 691072

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: 9.33e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;.
Eigen	Benign	0.087
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	0.058	D
MutationAssessor	Benign	1.5	L;.;L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.6	N;N;N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.22	B;D;D
Vest4		0.46
MutPred		0.53		.;Loss of disorder (P = 0.0112);.;
MVP		0.84
MPC		2.6
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.25
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr15-27017906;