rs6683133

Variant names:

• chr1-44667889-G-A
• rs6683133
• NM_024587.4:c.61+6442C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024587.4(TMEM53):​c.61+6442C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,876 control chromosomes in the GnomAD database, including 24,197 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24197 hom., cov: 30)
• Consequence: TMEM53 NM_024587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• Publications: 5 publications found

Genes affected

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

TMEM53 Gene-Disease associations (from GenCC):

• craniotubular dysplasia, Ikegawa type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• skeletal dysplasia

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024587.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM53	NM_024587.4	MANE Select	c.61+6442C>T		intron	N/A	NP_078863.2
	TMEM53	NM_001300747.2		c.61+6442C>T		intron	N/A	NP_001287676.1	Q5TDE2
	TMEM53	NM_001300748.2		c.61+6442C>T		intron	N/A	NP_001287677.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM53	ENST00000372237.8	TSL:1 MANE Select	c.61+6442C>T		intron	N/A	ENSP00000361311.3	Q6P2H8-1
	TMEM53	ENST00000476724.1	TSL:1	n.112+6442C>T		intron	N/A
	TMEM53	ENST00000372235.7	TSL:2	c.61+6442C>T		intron	N/A	ENSP00000361309.3	Q5TDE2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84790 AN: 151758 Hom.: 24176 Cov.: 30

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.560

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 84867 AN: 151876 Hom.: 24197 Cov.: 30 AF XY: 0.560 AC XY: 41543 AN XY: 74204

African (AFR) AF: 0.617 AC: 25529 AN: 41386

American (AMR) AF: 0.513 AC: 7828 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1133 AN: 5168

South Asian (SAS) AF: 0.466 AC: 2245 AN: 4818

European-Finnish (FIN) AF: 0.644 AC: 6782 AN: 10528

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37630 AN: 67936

Other (OTH) AF: 0.559 AC: 1177 AN: 2106

Alfa AF: 0.549 Hom.: 100619

Bravo AF: 0.552

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.4
DANN	Benign	0.57
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6683133; hg19: chr1-45133561;