8-90645755-C-A

Position:

• chr8-90645755-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000458549.7(TMEM64):​c.151G>T​(p.Gly51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G51R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM64 ENST00000458549.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0550

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]

LINC00534 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17582944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM64	NM_001008495.4	c.151G>T	p.Gly51Trp	missense_variant	1/3	ENST00000458549.7	NP_001008495.2
TMEM64	NM_001146273.1	c.151G>T	p.Gly51Trp	missense_variant	1/2		NP_001139745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM64	ENST00000458549.7	c.151G>T	p.Gly51Trp	missense_variant	1/3	1	NM_001008495.4	ENSP00000414786.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 923450 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 433028

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.151G>T (p.G51W) 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 151, causing the glycine (G) at amino acid position 51 to be replaced by a tryptophan (W). 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	0.27
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.58	T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.059
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.98	.;D
Vest4		0.34
MutPred		0.24		Loss of methylation at R48 (P = 0.0286);Loss of methylation at R48 (P = 0.0286);
MVP		0.030
MPC		3.1
ClinPred		0.70	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.15
gMVP		0.48

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.

Other links and lift over

hg19: chr8-91657983;