Variant 2-134456756-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_030923.5(TMEM163):c.830C>T(p.Pro277Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

TMEM163
NM_030923.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.85

Variant links:

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 links:

TMEM163 (HGNC:):

TMEM163 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM163	NM_030923.5 linkuse as main transcript	c.830C>T	p.Pro277Leu	missense_variant	8/8	ENST00000281924.6	NP_112185.1	Q8TC26-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM163	ENST00000281924.6 linkuse as main transcript	c.830C>T	p.Pro277Leu	missense_variant	8/8	1	NM_030923.5	ENSP00000281924.6	Q8TC26-1
TMEM163	ENST00000467316.1 linkuse as main transcript	n.1264C>T		non_coding_transcript_exon_variant	2/2	2
TMEM163	ENST00000476823.1 linkuse as main transcript	n.4086C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251074

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.830C>T (p.P277L) alteration is located in exon 8 (coding exon 8) of the TMEM163 gene. This alteration results from a C to T substitution at nucleotide position 830, causing the proline (P) at amino acid position 277 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.058

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.45

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.76

MutPred

0.44

Loss of loop (P = 0.0073);

MVP

0.31

MPC

1.6

ClinPred

0.90

GERP RS

5.6

Varity_R

0.35

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over