2-134590315-T-C

Variant names:

• chr2-134590315-T-C
• rs842360
• NM_030923.5:c.323-38224A>G

Variant summary

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

The NM_030923.5(TMEM163):​c.323-38224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,886 control chromosomes in the GnomAD database, including 15,519 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 0.44 (15519 hom., cov: 31)
• Consequence: TMEM163 NM_030923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 5 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 = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM163	NM_030923.5	c.323-38224A>G		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.323-38224A>G		intron_variant	Intron 2 of 7	1	NM_030923.5	ENSP00000281924.6

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66582 AN: 151768 Hom.: 15495 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.439 AC: 66635 AN: 151886 Hom.: 15519 Cov.: 31 AF XY: 0.447 AC XY: 33189 AN XY: 74222

African (AFR) AF: 0.423 AC: 17507 AN: 41386

American (AMR) AF: 0.563 AC: 8590 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2343 AN: 3464

East Asian (EAS) AF: 0.771 AC: 3969 AN: 5148

South Asian (SAS) AF: 0.551 AC: 2653 AN: 4812

European-Finnish (FIN) AF: 0.393 AC: 4148 AN: 10562

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25714 AN: 67948

Other (OTH) AF: 0.546 AC: 1151 AN: 2108

Alfa AF: 0.405 Hom.: 2091

Bravo AF: 0.453

Asia WGS AF: 0.651 AC: 2264 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	1.8
DANN	Benign	0.64
PhyloP100		-0.68
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: rs842360; hg19: chr2-135347885;