rs10483790

Variant names:

• chr14-66831452-C-T
• rs10483790
• NM_020806.5:c.294+6886C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020806.5(GPHN):​c.294+6886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 152,202 control chromosomes in the GnomAD database, including 187 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 0.043 (187 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 2 publications found

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]

GPHN Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020806.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPHN	NM_020806.5	MANE Select	c.294+6886C>T		intron	N/A	NP_065857.1	Q9NQX3-2
	GPHN	NM_001377514.1		c.294+6886C>T		intron	N/A	NP_001364443.1
	GPHN	NM_001377515.1		c.294+6886C>T		intron	N/A	NP_001364444.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPHN	ENST00000478722.6	TSL:1 MANE Select	c.294+6886C>T		intron	N/A	ENSP00000417901.1	Q9NQX3-2
	GPHN	ENST00000315266.9	TSL:1	c.294+6886C>T		intron	N/A	ENSP00000312771.5	Q9NQX3-1
	GPHN	ENST00000960384.1		c.294+6886C>T		intron	N/A	ENSP00000630443.1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6603 AN: 152084 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0434 AC: 6603 AN: 152202 Hom.: 187 Cov.: 32 AF XY: 0.0420 AC XY: 3124 AN XY: 74420

African (AFR) AF: 0.0115 AC: 480 AN: 41570

American (AMR) AF: 0.0400 AC: 612 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3470

East Asian (EAS) AF: 0.00793 AC: 41 AN: 5172

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4826

European-Finnish (FIN) AF: 0.0548 AC: 580 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0636 AC: 4324 AN: 67974

Other (OTH) AF: 0.0512 AC: 108 AN: 2110

Alfa AF: 0.0586 Hom.: 139

Bravo AF: 0.0407

Asia WGS AF: 0.0180 AC: 63 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.54
DANN	Benign	0.32
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10483790; hg19: chr14-67298170;