chr2-134635540-G-A

Variant names:

• chr2-134635540-G-A
• rs11684785
• NM_030923.5:c.322+77660C>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+77660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,976 control chromosomes in the GnomAD database, including 34,023 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 0.65 (34023 hom., cov: 31)
• Consequence: TMEM163 NM_030923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM163	NM_030923.5	c.322+77660C>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+77660C>T		intron_variant	Intron 2 of 7	1	NM_030923.5	ENSP00000281924.6

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99358 AN: 151858 Hom.: 33970 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.655 AC: 99473 AN: 151976 Hom.: 34023 Cov.: 31 AF XY: 0.646 AC XY: 47944 AN XY: 74270

African (AFR) AF: 0.820 AC: 33994 AN: 41444

American (AMR) AF: 0.578 AC: 8832 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5166

South Asian (SAS) AF: 0.469 AC: 2255 AN: 4810

European-Finnish (FIN) AF: 0.641 AC: 6759 AN: 10542

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43153 AN: 67976

Other (OTH) AF: 0.544 AC: 1141 AN: 2096

Alfa AF: 0.617 Hom.: 23292

Bravo AF: 0.655

Asia WGS AF: 0.415 AC: 1446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.74
PhyloP100		0.63
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: rs11684785; hg19: chr2-135393110;