2-134461034-A-G

Variant names:

• chr2-134461034-A-G
• rs6430516
• NM_030923.5:c.668-2861T>C

Variant summary

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

The NM_030923.5(TMEM163):​c.668-2861T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,958 control chromosomes in the GnomAD database, including 7,495 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 0.24 (7495 hom., cov: 32)
• Consequence: TMEM163 NM_030923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM163	NM_030923.5	c.668-2861T>C		intron_variant	Intron 6 of 7	ENST00000281924.6	NP_112185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM163	ENST00000281924.6	c.668-2861T>C		intron_variant	Intron 6 of 7	1	NM_030923.5	ENSP00000281924.6
TMEM163	ENST00000476823.1	n.3924-2861T>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37036 AN: 151840 Hom.: 7464 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.244 AC: 37133 AN: 151958 Hom.: 7495 Cov.: 32 AF XY: 0.243 AC XY: 18073 AN XY: 74296

African (AFR) AF: 0.522 AC: 21586 AN: 41328

American (AMR) AF: 0.184 AC: 2810 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2964 AN: 5158

South Asian (SAS) AF: 0.232 AC: 1121 AN: 4828

European-Finnish (FIN) AF: 0.0677 AC: 718 AN: 10602

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.0956 AC: 6498 AN: 67988

Other (OTH) AF: 0.236 AC: 496 AN: 2102

Alfa AF: 0.147 Hom.: 11091

Bravo AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.29
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: rs6430516; hg19: chr2-135218605;