rs9323475

Positions:

• chr14-66599451-C-G
• chr14-66599451-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020806.5(GPHN):​c.65-81656C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 136,028 control chromosomes in the GnomAD database, including 9,933 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9933 hom., cov: 22)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

Genes affected

GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPHN	NM_020806.5	c.65-81656C>G		intron_variant		ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6	c.65-81656C>G		intron_variant		1	NM_020806.5	ENSP00000417901

Frequencies

GnomAD3 genomes AF: 0.316 AC: 42931 AN: 135950 Hom.: 9910 Cov.: 22

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.304

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.316 AC: 42993 AN: 136028 Hom.: 9933 Cov.: 22 AF XY: 0.320 AC XY: 20921 AN XY: 65294

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.307

Alfa AF: 0.217 Hom.: 731

Bravo AF: 0.361

Asia WGS AF: 0.399 AC: 1374 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.50

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: rs9323475; hg19: chr14-67066169;