NM_014211.3:c.702A>C

Variant names:

• chr5-170808622-A-C
• rs892561406
• NM_014211.3:c.702A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014211.3(GABRP):​c.702A>C​(p.Leu234Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: GABRP NM_014211.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599

Genes affected

GABRP (HGNC:4089): (gamma-aminobutyric acid type A receptor subunit pi) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. The subunit encoded by this gene is expressed in several non-neuronal tissues including the uterus and ovaries. This subunit can assemble with known GABA A receptor subunits, and the presence of this subunit alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20858005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRP	NM_014211.3	c.702A>C	p.Leu234Phe	missense_variant	Exon 8 of 10	ENST00000265294.9	NP_055026.1
GABRP	NM_001291985.2	c.702A>C	p.Leu234Phe	missense_variant	Exon 8 of 9		NP_001278914.1
GABRP	XM_024446012.2	c.702A>C	p.Leu234Phe	missense_variant	Exon 8 of 10		XP_024301780.1
GABRP	XM_005265872.2	c.465A>C	p.Leu155Phe	missense_variant	Exon 6 of 8		XP_005265929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRP	ENST00000265294.9	c.702A>C	p.Leu234Phe	missense_variant	Exon 8 of 10	1	NM_014211.3	ENSP00000265294.4
GABRP	ENST00000518525.5	c.702A>C	p.Leu234Phe	missense_variant	Exon 9 of 11	5		ENSP00000430100.1
GABRP	ENST00000519598.1	c.702A>C	p.Leu234Phe	missense_variant	Exon 8 of 10	5		ENSP00000430772.1
GABRP	ENST00000519385.5	c.702A>C	p.Leu234Phe	missense_variant	Exon 8 of 9	2		ENSP00000430727.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74344

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.93	.;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.1	L;L;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.15	B;B;B;.
Vest4		0.38
MutPred		0.47		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.73
MPC		0.59
ClinPred		0.38	T
GERP RS		4.1
Varity_R		0.10
gMVP		0.56

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

Other links and lift over

dbSNP: rs892561406; hg19: chr5-170235626;