Variant chr1-44654677-C-CGGCGTGCCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_024587.4(TMEM53):c.715_716insTGGCACGCC(p.Leu236_Arg238dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00000684 in 1,461,826 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: 0.0000068 ( 0 hom. )

Consequence

TMEM53
NM_024587.4 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

Variant links:

Genes affected

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

TMEM53 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_024587.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM53	NM_024587.4 linkuse as main transcript	c.715_716insTGGCACGCC	p.Leu236_Arg238dup	inframe_insertion	3/3	ENST00000372237.8	NP_078863.2
TMEM53	NM_001300746.2 linkuse as main transcript	c.496_497insTGGCACGCC	p.Leu163_Arg165dup	inframe_insertion	2/2		NP_001287675.1
TMEM53	NM_001300747.2 linkuse as main transcript	c.625_626insTGGCACGCC	p.Leu206_Arg208dup	inframe_insertion	3/3		NP_001287676.1
TMEM53	NM_001300748.2 linkuse as main transcript	c.622_623insTGGCACGCC	p.Leu205_Arg207dup	inframe_insertion	3/3		NP_001287677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM53	ENST00000372237.8 linkuse as main transcript	c.715_716insTGGCACGCC	p.Leu236_Arg238dup	inframe_insertion	3/3	1	NM_024587.4	ENSP00000361311	P1	Q6P2H8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251382

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135882

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727216

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:

0.00

Gnomad4 NFE exome

AF:

0.00000899

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

Craniotubular dysplasia, Ikegawa type

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital

Jul 10, 2023

The novel homozygous variant c.707_715dup (p.Leu236_Arg238dup) has been identified in a proband with abnormal facial shape, abnormal vertebral morphology, abnormal visual electrophysiology, abnormality of limb bone morphology, acetabular dysplasia, brachydactyly, brain imaging abnormality, C1-C2 vertebral abnormality, calvarial hyperostosis, contractures of the joints of upper limbs, genu varum, optic atrophy, small hand, short foot, short humerus, short metacarpal, short metatarsal, short stature, microcephaly and scoliosis. This has been found in 0.0004% in gnomAD (aggregated) database (PM2_moderate). Protein length changes due to the deletion (PM4_moderate). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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