rs151322023

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020806.5(GPHN):c.633A>G(p.Gln211Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,613,606 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

GPHN
NM_020806.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00600

Publications

0 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 14-66922842-A-G is Benign according to our data. Variant chr14-66922842-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 466211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.006 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.000244 (357/1461428) while in subpopulation SAS AF = 0.0011 (95/86244). AF 95% confidence interval is 0.000922. There are 3 homozygotes in GnomAdExome4. There are 203 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHN	NM_020806.5 link	c.633A>G	p.Gln211Gln	synonymous_variant	Exon 7 of 23	ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6 link	c.633A>G	p.Gln211Gln	synonymous_variant	Exon 7 of 23	1	NM_020806.5	ENSP00000417901.1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000335

AC:

AN:

250990

AF XY:

0.000391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000244

AC:

357

AN:

1461428

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

203

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00110

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000159

AC:

177

AN:

1111618

Other (OTH)

AF:

0.000364

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000256

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41520

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00125

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68002

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000532

Hom.:

Bravo

AF:

0.000162

EpiCase

AF:

0.000654

EpiControl

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GPHN: BP4, BP7 -

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.56

CADD

Benign

2.6

(source)

DANN

Benign

0.42

PhyloP100

0.0060

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over