rs3759753

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020806.5(GPHN):c.65-9T>C variant causes a 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 intron

Scores

Splicing: ADA: 0.00009337

Clinical Significance

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

Conservation

PhyloP100: -0.180

Publications

9 publications found

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 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

GPHN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GPHN	NM_020806.5 link	c.65-9T>C		intron_variant	Intron 1 of 22	ENST00000478722.6	NP_065857.1	Q9NQX3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6 link	c.65-9T>C		intron_variant	Intron 1 of 22	1	NM_020806.5	ENSP00000417901.1		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

GnomAD2 exomes

AF:

0.266

AC:

66311

AN:

249382

AF XY:

0.251

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 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

African (AFR)

AF:

0.660

AC:

19714

AN:

29878

American (AMR)

AF:

0.421

AC:

18736

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

6006

AN:

25408

East Asian (EAS)

AF:

0.441

AC:

17142

AN:

38892

South Asian (SAS)

AF:

0.302

AC:

25237

AN:

83600

European-Finnish (FIN)

AF:

0.149

AC:

7825

AN:

52518

Middle Eastern (MID)

AF:

0.291

AC:

1386

AN:

4758

European-Non Finnish (NFE)

AF:

0.124

AC:

126456

AN:

1023580

Other (OTH)

AF:

0.214

AC:

12104

AN:

56520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

7704

15409

23113

30818

38522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4800

9600

14400

19200

24000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.328

AC:

49798

AN:

151938

Hom.:

11976

Cov.:

AF XY:

0.331

AC XY:

24592

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.655

AC:

27090

AN:

41384

American (AMR)

AF:

0.386

AC:

5886

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3466

East Asian (EAS)

AF:

0.468

AC:

2418

AN:

5164

South Asian (SAS)

AF:

0.326

AC:

1575

AN:

4828

European-Finnish (FIN)

AF:

0.154

AC:

1630

AN:

10570

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9430

AN:

67940

Other (OTH)

AF:

0.318

AC:

673

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1310

2620

3930

5240

6550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.232

Hom.:

10061

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

(source)

DANN

Benign

0.41

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over