4-174828785-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006529.4(GLRA3):c.27A>T(p.Thr9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,611,562 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (6 hom.)
• Consequence: GLRA3 NM_006529.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0920

Genes affected

GLRA3 (HGNC:4328): (glycine receptor alpha 3) This gene encodes a member of the ligand-gated ion channel protein family. The encoded protein is a member of the glycine receptor subfamily. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 4-174828785-T-A is Benign according to our data. Variant chr4-174828785-T-A is described in ClinVar as [Benign]. Clinvar id is 781993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.092 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA3	NM_006529.4	c.27A>T	p.Thr9=	synonymous_variant	1/10	ENST00000274093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA3	ENST00000274093.8	c.27A>T	p.Thr9=	synonymous_variant	1/10	1	NM_006529.4
GLRA3	ENST00000340217.5	c.27A>T	p.Thr9=	synonymous_variant	1/9	1		P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152172 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00188 AC: 473 AN: 251430 Hom.: 2 AF XY: 0.00169 AC XY: 229 AN XY: 135892

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.00427

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00211

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00213 AC: 3110 AN: 1459272 Hom.: 6 Cov.: 28 AF XY: 0.00207 AC XY: 1500 AN XY: 726174

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00483

Gnomad4 ASJ exome AF: 0.00429

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.00233

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152290 Hom.: 2 Cov.: 33 AF XY: 0.00183 AC XY: 136 AN XY: 74478

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00232 Hom.: 0

Bravo AF: 0.00254

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	6.2
Dann	Benign	0.84

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: rs139727969; hg19: chr4-175749936; COSMIC: COSV56862792; COSMIC: COSV56862792;