Variant rs77465022 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020806.5(GPHN):c.1734T>C(p.Gly578=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,613,186 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 42 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 22 hom. )

Consequence

GPHN
NM_020806.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.774

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:

LOC105370538 (HGNC:):

LOC105370538 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-67122363-T-C is Benign according to our data. Variant chr14-67122363-T-C is described in ClinVar as [Benign]. Clinvar id is 466202.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.774 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1707/152260) while in subpopulation AFR AF= 0.0375 (1559/41550). AF 95% confidence interval is 0.036. There are 42 homozygotes in gnomad4. There are 789 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPHN	NM_020806.5 linkuse as main transcript	c.1734T>C	p.Gly578=	synonymous_variant	17/23	ENST00000478722.6
LOC105370538	XR_007064215.1 linkuse as main transcript	n.224-13901A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPHN	ENST00000478722.6 linkuse as main transcript	c.1734T>C	p.Gly578=	synonymous_variant	17/23	1	NM_020806.5		Q9NQX3-2

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1704

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00312

AC:

784

AN:

251316

Hom.:

AF XY:

0.00222

AC XY:

302

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00129

AC:

1887

AN:

1460926

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

839

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.0406

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.0112

AC:

1707

AN:

152260

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

789

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0375

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00520

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.4

DANN

Benign

0.72

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

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