rs376426309

Variant names:

• chr5-151924500-A-C
• NM_000171.4:c.50T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-151924500-A-C
• chr5-151924500-A-G

Variant summary

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

The NM_001292000.2(GLRA1):​c.-72T>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000696 in 1,435,888 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: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GLRA1 NM_001292000.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81

Genes affected

GLRA1 (HGNC:4326): (glycine receptor alpha 1) The protein encoded by this gene is a subunit of a pentameric inhibitory glycine receptor, which mediates postsynaptic inhibition in the central nervous system. Defects in this gene are a cause of startle disease (STHE), also known as hereditary hyperekplexia or congenital stiff-person syndrome. Multiple transcript variants encoding different isoforms have been found. [provided by RefSeq, Dec 2015]

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
GLRA1	NM_000171.4	c.50T>G	p.Phe17Cys	missense_variant	Exon 1 of 9	ENST00000274576.9	NP_000162.2
GLRA1	NM_001292000.2	c.-72T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8		NP_001278929.1
GLRA1	NM_001146040.2	c.50T>G	p.Phe17Cys	missense_variant	Exon 1 of 9		NP_001139512.1
GLRA1	NM_001292000.2	c.-72T>G		5_prime_UTR_variant	Exon 1 of 8		NP_001278929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.50T>G	p.Phe17Cys	missense_variant	Exon 1 of 9	1	NM_000171.4	ENSP00000274576.5
GLRA1	ENST00000455880.2	c.50T>G	p.Phe17Cys	missense_variant	Exon 1 of 9	1		ENSP00000411593.2
GLRA1	ENST00000462581.6	n.50T>G		non_coding_transcript_exon_variant	Exon 1 of 8	1		ENSP00000430595.1
GLRA1	ENST00000471351.2	n.333T>G		non_coding_transcript_exon_variant	Exon 1 of 8	1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1435888 Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1 AN XY: 716362

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.56	N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.049	D;T
Polyphen		0.95	P;P
Vest4		0.56
MutPred		0.43		Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.80
MPC		.;3.98175777942E-4
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.60

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: chr5-151304061;