Variant 14-66824468-T-C 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 ENST00000478722.6(GPHN):c.202-6T>C variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.101 in 1,515,180 control chromosomes in the GnomAD database, including 24,680 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 8271 hom., cov: 32)

Exomes 𝑓: 0.086 ( 16409 hom. )

Consequence

GPHN
ENST00000478722.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005558

Clinical Significance

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

Conservation

PhyloP100: 4.31

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=-0.51).

BP6

Variant 14-66824468-T-C is Benign according to our data. Variant chr14-66824468-T-C is described in ClinVar as [Benign]. Clinvar id is 261354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 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.202-6T>C		splice_region_variant, 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.202-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020806.5	ENSP00000417901		Q9NQX3-2

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35569

AN:

151870

Hom.:

8264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.0821

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.0826

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.184

AC:

45943

AN:

250310

Hom.:

8538

AF XY:

0.169

AC XY:

22823

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.0846

Gnomad EAS exome

AF:

0.461

Gnomad SAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.0774

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.0864

AC:

117770

AN:

1363192

Hom.:

16409

Cov.:

AF XY:

0.0889

AC XY:

60852

AN XY:

684388

show subpopulations

Gnomad4 AFR exome

AF:

0.574

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.0843

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.0781

Gnomad4 NFE exome

AF:

0.0313

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.234

AC:

35621

AN:

151988

Hom.:

8271

Cov.:

AF XY:

0.240

AC XY:

17807

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.563

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.0821

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.0826

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.0829

Hom.:

3434

Bravo

AF:

0.267

Asia WGS

AF:

0.340

AC:

1182

AN:

3474

EpiCase

AF:

0.0471

EpiControl

AF:

0.0446

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

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

-0.51

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000056

dbscSNV1_RF

Benign

0.012

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