Variant 8-90645586-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001008495.4(TMEM64):c.320G>T(p.Arg107Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,389,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

TMEM64
NM_001008495.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

TMEM64 (HGNC:25441): (transmembrane protein 64) Predicted to be involved in negative regulation of canonical Wnt signaling pathway; negative regulation of osteoblast differentiation; and positive regulation of fat cell differentiation. Predicted to act upstream of or within several processes, including positive regulation of bone resorption; positive regulation of osteoclast differentiation; and regulation of ATPase activity. Predicted to be located in endoplasmic reticulum. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM64 links:

LINC00534 (HGNC:43643): (long intergenic non-protein coding RNA 534)

LINC00534 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29108217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM64	NM_001008495.4 link	c.320G>T	p.Arg107Ile	missense_variant	1/3	ENST00000458549.7	NP_001008495.2	Q6YI46-1
TMEM64	NM_001146273.1 link	c.320G>T	p.Arg107Ile	missense_variant	1/2		NP_001139745.1	Q6YI46-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM64	ENST00000458549.7 link	c.320G>T	p.Arg107Ile	missense_variant	1/3	1	NM_001008495.4	ENSP00000414786.2		Q6YI46-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1389482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685584

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:

0.0000249

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 28, 2024

The c.320G>T (p.R107I) alteration is located in exon 1 (coding exon 1) of the TMEM64 gene. This alteration results from a G to T substitution at nucleotide position 320, causing the arginine (R) at amino acid position 107 to be replaced by an isoleucine (I). 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

Benign

0.29

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.059

.;T

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.75

T;T

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

L;L

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

.;D

Vest4

0.48

MutPred

0.44

Loss of MoRF binding (P = 0.0683);Loss of MoRF binding (P = 0.0683);

MVP

0.081

MPC

4.9

ClinPred

0.88

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.17

gMVP

0.45

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over