rs9323475

Variant names:

• chr14-66599451-C-G
• rs9323475
• NM_020806.5:c.65-81656C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-66599451-C-G
• chr14-66599451-C-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.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
• 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: 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 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.65-81656C>G		intron	N/A	NP_065857.1	Q9NQX3-2
	GPHN	NM_001377514.1		c.65-81656C>G		intron	N/A	NP_001364443.1
	GPHN	NM_001377515.1		c.65-81656C>G		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.65-81656C>G		intron	N/A	ENSP00000417901.1	Q9NQX3-2
	GPHN	ENST00000315266.9	TSL:1	c.65-81656C>G		intron	N/A	ENSP00000312771.5	Q9NQX3-1
	GPHN	ENST00000960384.1		c.65-81656C>G		intron	N/A	ENSP00000630443.1

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

African (AFR) AF: 0.652 AC: 22883 AN: 35074

American (AMR) AF: 0.379 AC: 5066 AN: 13352

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 771 AN: 3358

East Asian (EAS) AF: 0.463 AC: 2135 AN: 4614

South Asian (SAS) AF: 0.311 AC: 1321 AN: 4248

European-Finnish (FIN) AF: 0.138 AC: 1070 AN: 7768

Middle Eastern (MID) AF: 0.248 AC: 67 AN: 270

European-Non Finnish (NFE) AF: 0.137 AC: 8876 AN: 64584

Other (OTH) AF: 0.307 AC: 582 AN: 1896

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-0.064
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: rs9323475; hg19: chr14-67066169;