XM_047430879.1:c.1313-130342C>T

Variant names:

• chr14-67604853-C-T
• rs12885261
• XM_047430879.1:c.1313-130342C>T

Variant summary

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

The XM_047430879.1(GPHN):​c.1313-130342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,858 control chromosomes in the GnomAD database, including 15,993 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 0.45 (15993 hom., cov: 31)
• Consequence: GPHN XM_047430879.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHN	XM_047430879.1	c.1313-130342C>T		intron_variant	Intron 14 of 14		XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68924 AN: 151740 Hom.: 15965 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.454 AC: 69007 AN: 151858 Hom.: 15993 Cov.: 31 AF XY: 0.457 AC XY: 33903 AN XY: 74212

African (AFR) AF: 0.492 AC: 20358 AN: 41372

American (AMR) AF: 0.566 AC: 8623 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1260 AN: 3460

East Asian (EAS) AF: 0.434 AC: 2245 AN: 5174

South Asian (SAS) AF: 0.451 AC: 2169 AN: 4810

European-Finnish (FIN) AF: 0.383 AC: 4038 AN: 10536

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28828 AN: 67946

Other (OTH) AF: 0.452 AC: 953 AN: 2108

Alfa AF: 0.434 Hom.: 9883

Bravo AF: 0.473

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12885261; hg19: chr14-68071570;