rs3784075

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.202-6T>C variant causes a splice region, 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
NM_020806.5 splice_region, intron

Scores

Splicing: ADA: 0.00005558

Clinical Significance

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

Conservation

PhyloP100: 4.31

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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
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=-0.51).

BP6

Variant 14-66824468-T-C is Benign according to our data. Variant chr14-66824468-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020806.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPHN	NM_020806.5	MANE Select	c.202-6T>C	splice_region intron	N/A	NP_065857.1	Q9NQX3-2
GPHN	NM_001377514.1		c.202-6T>C	splice_region intron	N/A	NP_001364443.1
GPHN	NM_001377515.1		c.202-6T>C	splice_region intron	N/A	NP_001364444.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPHN	ENST00000478722.6	TSL:1 MANE Select	c.202-6T>C	splice_region intron	N/A	ENSP00000417901.1	Q9NQX3-2
GPHN	ENST00000315266.9	TSL:1	c.202-6T>C	splice_region intron	N/A	ENSP00000312771.5	Q9NQX3-1
GPHN	ENST00000960384.1		c.202-6T>C	splice_region intron	N/A	ENSP00000630443.1

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

GnomAD2 exomes

AF:

0.184

AC:

45943

AN:

250310

AF XY:

0.169

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 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

African (AFR)

AF:

0.574

AC:

17617

AN:

30710

American (AMR)

AF:

0.359

AC:

15991

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.0843

AC:

2150

AN:

25506

East Asian (EAS)

AF:

0.430

AC:

16732

AN:

38920

South Asian (SAS)

AF:

0.251

AC:

21038

AN:

83794

European-Finnish (FIN)

AF:

0.0781

AC:

4166

AN:

53328

Middle Eastern (MID)

AF:

0.160

AC:

888

AN:

5534

European-Non Finnish (NFE)

AF:

0.0313

AC:

32061

AN:

1023950

Other (OTH)

AF:

0.125

AC:

7127

AN:

56964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3889

7779

11668

15558

19447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1828

3656

5484

7312

9140

<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:

0.234

AC:

35621

AN:

151988

Hom.:

8271

Cov.:

AF XY:

0.240

AC XY:

17807

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.563

AC:

23295

AN:

41386

American (AMR)

AF:

0.296

AC:

4517

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0821

AC:

285

AN:

3472

East Asian (EAS)

AF:

0.458

AC:

2359

AN:

5154

South Asian (SAS)

AF:

0.282

AC:

1361

AN:

4822

European-Finnish (FIN)

AF:

0.0826

AC:

876

AN:

10604

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0359

AC:

2443

AN:

67978

Other (OTH)

AF:

0.213

AC:

450

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

949

1897

2846

3794

4743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.117

Hom.:

9551

Bravo

AF:

0.267

Asia WGS

AF:

0.340

AC:

1182

AN:

3474

EpiCase

AF:

0.0471

EpiControl

AF:

0.0446

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

4.3

PromoterAI

-0.021

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over