rs10179686

Variant names:

• chr2-134456999-C-T
• rs10179686
• NM_030923.5:c.810-223G>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.810-223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 151,990 control chromosomes in the GnomAD database, including 577 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 0.070 (577 hom., cov: 32)
• Consequence: TMEM163 NM_030923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM163	NM_030923.5	c.810-223G>A		intron_variant	Intron 7 of 7	ENST00000281924.6	NP_112185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM163	ENST00000281924.6	c.810-223G>A		intron_variant	Intron 7 of 7	1	NM_030923.5	ENSP00000281924.6
TMEM163	ENST00000467316.1	n.1244-223G>A		intron_variant	Intron 1 of 1	2
TMEM163	ENST00000476823.1	n.4066-223G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10642 AN: 151870 Hom.: 570 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0701 AC: 10660 AN: 151990 Hom.: 577 Cov.: 32 AF XY: 0.0720 AC XY: 5348 AN XY: 74252

African (AFR) AF: 0.102 AC: 4234 AN: 41444

American (AMR) AF: 0.0683 AC: 1043 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1300 AN: 5168

South Asian (SAS) AF: 0.0860 AC: 413 AN: 4802

European-Finnish (FIN) AF: 0.0474 AC: 501 AN: 10566

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.0373 AC: 2533 AN: 67944

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0548 Hom.: 65

Bravo AF: 0.0768

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.63
PhyloP100		-0.12
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: rs10179686; hg19: chr2-135214570;