14-66680999-GA-G

Position:

• chr14-66680999-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020806.5(GPHN):​c.65-97del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 525,440 control chromosomes in the GnomAD database, including 12,312 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (6683 hom., cov: 25)
  • Exomes 𝑓: 0.17 (5629 hom.)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0610

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 -10 ACMG points.

• BP6: Variant 14-66680999-GA-G is Benign according to our data. Variant chr14-66680999-GA-G is described in ClinVar as [Benign]. Clinvar id is 1182217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPHN	NM_020806.5	c.65-97del		intron_variant		ENST00000478722.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPHN	ENST00000478722.6	c.65-97del		intron_variant		1	NM_020806.5

Frequencies

GnomAD3 genomes AF: 0.230 AC: 32784 AN: 142746 Hom.: 6648 Cov.: 25

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.0748

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.0854

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.171 AC: 65587 AN: 382592 Hom.: 5629 AF XY: 0.175 AC XY: 36278 AN XY: 207174

Gnomad4 AFR exome AF: 0.492

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0921

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.230 AC: 32881 AN: 142848 Hom.: 6683 Cov.: 25 AF XY: 0.237 AC XY: 16387 AN XY: 69270

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.0748

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.0854

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.223

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs10711873; hg19: chr14-67147717;