2-134699189-C-T

Variant names:

• chr2-134699189-C-T
• rs10928513
• NM_030923.5:c.322+14011G>A

Variant summary

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

The NM_030923.5(TMEM163):​c.322+14011G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,202 control chromosomes in the GnomAD database, including 41,721 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 0.72 (41721 hom., cov: 33)
• Consequence: TMEM163 NM_030923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 9 publications found

Genes affected

TMEM163 (HGNC:25380): (transmembrane protein 163) Predicted to enable zinc ion binding activity. Predicted to be involved in zinc ion import into synaptic vesicle. Predicted to be located in early endosome membrane. Predicted to be active in intracellular vesicle and plasma membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM163 Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 25

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM163	NM_030923.5	c.322+14011G>A		intron_variant	Intron 2 of 7	ENST00000281924.6	NP_112185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM163	ENST00000281924.6	c.322+14011G>A		intron_variant	Intron 2 of 7	1	NM_030923.5	ENSP00000281924.6

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109132 AN: 152084 Hom.: 41656 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.718 AC: 109257 AN: 152202 Hom.: 41721 Cov.: 33 AF XY: 0.726 AC XY: 54005 AN XY: 74394

African (AFR) AF: 0.917 AC: 38121 AN: 41572

American (AMR) AF: 0.782 AC: 11963 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3162 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5184 AN: 5192

South Asian (SAS) AF: 0.889 AC: 4286 AN: 4820

European-Finnish (FIN) AF: 0.584 AC: 6157 AN: 10550

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37963 AN: 67994

Other (OTH) AF: 0.790 AC: 1665 AN: 2108

Alfa AF: 0.602 Hom.: 6976

Bravo AF: 0.742

Asia WGS AF: 0.942 AC: 3275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.47
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10928513; hg19: chr2-135456759;