rs10483791

Variant names:

• chr14-66984791-C-T
• rs10483791
• NM_020806.5:c.963+19466C>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.963+19466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 151,998 control chromosomes in the GnomAD database, including 568 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 0.074 (568 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• 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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHN	NM_020806.5	c.963+19466C>T		intron_variant	Intron 9 of 22	ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6	c.963+19466C>T		intron_variant	Intron 9 of 22	1	NM_020806.5	ENSP00000417901.1

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11232 AN: 151880 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0772

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

GnomAD4 genome AF: 0.0739 AC: 11229 AN: 151998 Hom.: 568 Cov.: 32 AF XY: 0.0703 AC XY: 5220 AN XY: 74284

African (AFR) AF: 0.0210 AC: 872 AN: 41504

American (AMR) AF: 0.0503 AC: 767 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5170

South Asian (SAS) AF: 0.0786 AC: 379 AN: 4822

European-Finnish (FIN) AF: 0.0650 AC: 686 AN: 10548

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.118 AC: 8026 AN: 67922

Other (OTH) AF: 0.0759 AC: 160 AN: 2108

Alfa AF: 0.0940 Hom.: 275

Bravo AF: 0.0703

Asia WGS AF: 0.0310 AC: 110 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs10483791; hg19: chr14-67451508;