XR_007064213.1:n.9019G>T

Variant names:

• chr14-67452966-C-A
• rs7156173
• XR_007064213.1:n.9019G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007064213.1(LOC105370542):​n.9019G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,128 control chromosomes in the GnomAD database, including 3,873 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 0.20 (3873 hom., cov: 32)
• Consequence: LOC105370542 XR_007064213.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 1 publications found

Genes affected

LOC105370542 (HGNC:):

TMEM229B (HGNC:20130): (transmembrane protein 229B) Predicted to act upstream of or within response to bacterium. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370542	XR_007064213.1	n.9019G>T		non_coding_transcript_exon_variant	Exon 3 of 3
LOC105370542	XR_007064214.1	n.8425G>T		non_coding_transcript_exon_variant	Exon 3 of 3
LOC105370542	XR_943964.3	n.3196G>T		non_coding_transcript_exon_variant	Exon 3 of 3
GPHN	XM_047430879.1	c.1313-282229C>A		intron_variant	Intron 14 of 14		XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM229B	ENST00000555638.5	n.*1132+1114G>T		intron_variant	Intron 7 of 8	2		ENSP00000452201.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30319 AN: 152010 Hom.: 3866 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.200 AC: 30360 AN: 152128 Hom.: 3873 Cov.: 32 AF XY: 0.198 AC XY: 14746 AN XY: 74388

African (AFR) AF: 0.364 AC: 15090 AN: 41448

American (AMR) AF: 0.223 AC: 3413 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3472

East Asian (EAS) AF: 0.147 AC: 761 AN: 5170

South Asian (SAS) AF: 0.180 AC: 871 AN: 4830

European-Finnish (FIN) AF: 0.0872 AC: 925 AN: 10612

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8115 AN: 68008

Other (OTH) AF: 0.199 AC: 419 AN: 2110

Alfa AF: 0.141 Hom.: 2470

Bravo AF: 0.214

Asia WGS AF: 0.201 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7156173; hg19: chr14-67919683;