rs6745983

Variant names:

• chr2-134673139-G-A
• rs6745983
• NM_030923.5:c.322+40061C>T

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+40061C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,898 control chromosomes in the GnomAD database, including 23,299 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 0.54 (23299 hom., cov: 31)
• Consequence: TMEM163 NM_030923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 13 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM163	NM_030923.5	c.322+40061C>T		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+40061C>T		intron_variant	Intron 2 of 7	1	NM_030923.5	ENSP00000281924.6

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82156 AN: 151780 Hom.: 23286 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.541 AC: 82217 AN: 151898 Hom.: 23299 Cov.: 31 AF XY: 0.533 AC XY: 39578 AN XY: 74232

African (AFR) AF: 0.631 AC: 26127 AN: 41424

American (AMR) AF: 0.478 AC: 7305 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3464

East Asian (EAS) AF: 0.211 AC: 1090 AN: 5168

South Asian (SAS) AF: 0.310 AC: 1486 AN: 4794

European-Finnish (FIN) AF: 0.555 AC: 5839 AN: 10514

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37919 AN: 67948

Other (OTH) AF: 0.429 AC: 904 AN: 2106

Alfa AF: 0.526 Hom.: 11923

Bravo AF: 0.540

Asia WGS AF: 0.291 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.6
DANN	Benign	0.73
PhyloP100		0.31
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: rs6745983; hg19: chr2-135430709;