Variant rs3759753 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020806.5(GPHN):c.65-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,511,636 control chromosomes in the GnomAD database, including 41,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 11976 hom., cov: 32)

Exomes 𝑓: 0.17 ( 29859 hom. )

Consequence

GPHN
NM_020806.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009337

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.180

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 14-66681098-T-C is Benign according to our data. Variant chr14-66681098-T-C is described in ClinVar as [Benign]. Clinvar id is 261355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPHN	NM_020806.5 linkuse as main transcript	c.65-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6 linkuse as main transcript	c.65-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_020806.5	ENSP00000417901		Q9NQX3-2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49694

AN:

151820

Hom.:

11937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.654

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.315

GnomAD3 exomes

AF:

0.266

AC:

66311

AN:

249382

Hom.:

12298

AF XY:

0.251

AC XY:

33872

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.666

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.464

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.173

AC:

234606

AN:

1359698

Hom.:

29859

Cov.:

AF XY:

0.175

AC XY:

119238

AN XY:

682310

show subpopulations

Gnomad4 AFR exome

AF:

0.660

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.441

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.328

AC:

49798

AN:

151938

Hom.:

11976

Cov.:

AF XY:

0.331

AC XY:

24592

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.468

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.188

Hom.:

4309

Bravo

AF:

0.361

Asia WGS

AF:

0.401

AC:

1391

AN:

3470

EpiCase

AF:

0.155

EpiControl

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 08, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000093

dbscSNV1_RF

Benign

0.024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over