5-161689680-C-A

Variant names:

• chr5-161689680-C-A
• NM_000811.3:c.574C>A

Variant summary

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

The NM_000811.3(GABRA6):​c.574C>A​(p.Pro192Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABRA6 NM_000811.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

Genes affected

GABRA6 (HGNC:4080): (gamma-aminobutyric acid type A receptor subunit alpha6) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]

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
GABRA6	NM_000811.3	c.574C>A	p.Pro192Thr	missense_variant	Exon 6 of 9	ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10	c.574C>A	p.Pro192Thr	missense_variant	Exon 6 of 9	1	NM_000811.3	ENSP00000274545.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.574C>A (p.P192T) alteration is located in exon 6 (coding exon 6) of the GABRA6 gene. This alteration results from a C to A substitution at nucleotide position 574, causing the proline (P) at amino acid position 192 to be replaced by a threonine (T). 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	0.19
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.66	D;D;D;D
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Benign	1.6	L;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Uncertain	0.40
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.072	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.70
MutPred		0.35		Gain of sheet (P = 0.0827);.;.;.;
MVP		0.85
MPC		0.44
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.46
gMVP		0.43

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.

Other links and lift over

hg19: chr5-161116686;