Variant 2-73385903-TGGAGGAGGAGGAGGAGGAGGAGGA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3

The NM_001378454.1(ALMS1):c.51_74delGGAGGAGGAGGAGGAGGAGGAGGA(p.Glu18_Glu25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 701,270 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

ALMS1
NM_001378454.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.45

Variant links:

Genes affected

ALMS1 (HGNC:428): (ALMS1 centrosome and basal body associated protein) This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]

ALMS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001378454.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALMS1	NM_001378454.1 link	c.51_74delGGAGGAGGAGGAGGAGGAGGAGGA	p.Glu18_Glu25del	disruptive_inframe_deletion	1/23	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 link	c.51_74delGGAGGAGGAGGAGGAGGAGGAGGA	p.Glu18_Glu25del	disruptive_inframe_deletion	1/23		NP_055935.4	Q8TCU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 link	c.51_74delGGAGGAGGAGGAGGAGGAGGAGGA	p.Glu18_Glu25del	disruptive_inframe_deletion	1/23	1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.0000557

AC:

AN:

143532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000234

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000622

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000412

AC:

AN:

557738

Hom.:

AF XY:

0.0000504

AC XY:

AN XY:

297828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000357

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000385

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000557

AC:

AN:

143532

Hom.:

Cov.:

AF XY:

0.0000431

AC XY:

AN XY:

69544

show subpopulations

Gnomad4 AFR

AF:

0.0000251

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000234

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000622

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge -

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 11, 2024

The c.51_77del27 variant (also known as p.E21_E29del) is located in coding exon 1 of the ALMS1 gene. This variant results from an in-frame GGAGGAGGAGGAGGAGGAGGAGGAAGA deletion at nucleotide positions 51 to 77. This results in the in-frame deletion of a at codon 21. This amino acid position ranges from well conserved to poorly conserved in available vertebrate species. This in-frame variant is in a repetitive region of the gene and has no known function or association with disease. Based on the available evidence, the clinical significance of this variant remains unclear. -

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

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