chr1-44654602-G-A

Position:

• chr1-44654602-G-A

Variant summary

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

The NM_024587.4(TMEM53):​c.791C>T​(p.Thr264Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM53 NM_024587.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95

Genes affected

TMEM53 (HGNC:26186): (transmembrane protein 53) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2249408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM53	NM_024587.4	c.791C>T	p.Thr264Ile	missense_variant	3/3	ENST00000372237.8	NP_078863.2
TMEM53	NM_001300747.2	c.701C>T	p.Thr234Ile	missense_variant	3/3		NP_001287676.1
TMEM53	NM_001300748.2	c.698C>T	p.Thr233Ile	missense_variant	3/3		NP_001287677.1
TMEM53	NM_001300746.2	c.572C>T	p.Thr191Ile	missense_variant	2/2		NP_001287675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM53	ENST00000372237.8	c.791C>T	p.Thr264Ile	missense_variant	3/3	1	NM_024587.4	ENSP00000361311	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

May 23, 2023

The c.791C>T (p.T264I) alteration is located in exon 3 (coding exon 3) of the TMEM53 gene. This alteration results from a C to T substitution at nucleotide position 791, causing the threonine (T) at amino acid position 264 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	0.21
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0097	T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	0.83	D;D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.086
Sift	Benign	0.15	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.71	P;.
Vest4		0.31
MutPred		0.58		Gain of helix (P = 0.2294);.;
MVP		0.12
MPC		0.96
ClinPred		0.85	D
GERP RS		5.0
Varity_R		0.075
gMVP		0.53

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: chr1-45120274;