rs1554083817

Variant names:

• chr5-151855127-C-A
• NM_000171.4:c.610G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151855127-C-A
• chr5-151855127-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000171.4(GLRA1):​c.610G>T​(p.Val204Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GLRA1 NM_000171.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.70

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA1	NM_000171.4	c.610G>T	p.Val204Leu	missense_variant	Exon 6 of 9	ENST00000274576.9	NP_000162.2
GLRA1	NM_001146040.2	c.610G>T	p.Val204Leu	missense_variant	Exon 6 of 9		NP_001139512.1
GLRA1	NM_001292000.2	c.361G>T	p.Val121Leu	missense_variant	Exon 5 of 8		NP_001278929.1
GLRA1	XM_047417105.1	c.658G>T	p.Val220Leu	missense_variant	Exon 6 of 9		XP_047273061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.610G>T	p.Val204Leu	missense_variant	Exon 6 of 9	1	NM_000171.4	ENSP00000274576.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461514 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727080

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Pathogenic	0.66
Sift	Benign	0.037	D;D
Sift4G	Benign	0.063	T;T
Polyphen		1.0	D;D
Vest4		0.75
MutPred		0.53		Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);
MVP		0.75
MPC		1.9
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.69
gMVP		0.69

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: chr5-151234688;