14-66682221-T-C

Variant names:

• chr14-66682221-T-C
• rs9783601
• NM_020806.5:c.143+1036T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020806.5(GPHN):​c.143+1036T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,094 control chromosomes in the GnomAD database, including 11,185 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (11185 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHN	NM_020806.5	c.143+1036T>C		intron_variant	Intron 2 of 22	ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6	c.143+1036T>C		intron_variant	Intron 2 of 22	1	NM_020806.5	ENSP00000417901.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47238 AN: 151976 Hom.: 11169 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.311 AC: 47307 AN: 152094 Hom.: 11185 Cov.: 32 AF XY: 0.314 AC XY: 23344 AN XY: 74350

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.294

Alfa AF: 0.161 Hom.: 2395

Bravo AF: 0.345

Asia WGS AF: 0.367 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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

Other links and lift over

dbSNP: rs9783601; hg19: chr14-67148939;