1-44654756-G-A

Position:

• chr1-44654756-G-A

Variant summary

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

The NM_024587.4(TMEM53):​c.637C>T​(p.Leu213Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.58

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM53	NM_024587.4	c.637C>T	p.Leu213Phe	missense_variant	3/3	ENST00000372237.8	NP_078863.2
TMEM53	NM_001300747.2	c.547C>T	p.Leu183Phe	missense_variant	3/3		NP_001287676.1
TMEM53	NM_001300748.2	c.544C>T	p.Leu182Phe	missense_variant	3/3		NP_001287677.1
TMEM53	NM_001300746.2	c.418C>T	p.Leu140Phe	missense_variant	2/2		NP_001287675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM53	ENST00000372237.8	c.637C>T	p.Leu213Phe	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

Jun 10, 2024

The c.637C>T (p.L213F) 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 637, causing the leucine (L) at amino acid position 213 to be replaced by a phenylalanine (F). 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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.34
Sift	Benign	0.038	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.98	D;.
Vest4		0.15
MutPred		0.95		Loss of sheet (P = 0.1158);.;
MVP		0.15
MPC		1.4
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.33
gMVP		0.84

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: chr1-45120428;