chr14-67165222-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_020806.5(GPHN):c.1971A>C(p.Leu657Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,595,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

GPHN
NM_020806.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.122

Publications

1 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:

ENSG00000307479 (HGNC:):

ENSG00000307479 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 14-67165222-A-C is Benign according to our data. Variant chr14-67165222-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 466205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.122 with no splicing effect.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
GPHN	NM_020806.5	MANE Select	c.1971A>C	p.Leu657Leu	synonymous	Exon 20 of 23	NP_065857.1	Q9NQX3-2
GPHN	NM_001377514.1		c.2031A>C	p.Leu677Leu	synonymous	Exon 22 of 25	NP_001364443.1
GPHN	NM_001377515.1		c.2001A>C	p.Leu667Leu	synonymous	Exon 21 of 24	NP_001364444.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPHN	ENST00000478722.6	TSL:1 MANE Select	c.1971A>C	p.Leu657Leu	synonymous	Exon 20 of 23	ENSP00000417901.1	Q9NQX3-2
GPHN	ENST00000315266.9	TSL:1	c.1872A>C	p.Leu624Leu	synonymous	Exon 19 of 22	ENSP00000312771.5	Q9NQX3-1
GPHN	ENST00000960384.1		c.2142A>C	p.Leu714Leu	synonymous	Exon 22 of 25	ENSP00000630443.1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000239

AC:

AN:

251086

AF XY:

0.000287

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000485

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000484

AC:

699

AN:

1443720

Hom.:

Cov.:

AF XY:

0.000481

AC XY:

346

AN XY:

719468

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

33100

American (AMR)

AF:

0.0000224

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.00

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000616

AC:

675

AN:

1095520

Other (OTH)

AF:

0.000268

AC:

AN:

59804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<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:

0.000158

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000294

Hom.:

Bravo

AF:

0.000246

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

GPHN-related disorder (1)

not provided (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

-0.39

CADD

Benign

8.6

(source)

DANN

Benign

0.81

PhyloP100

0.12

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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