rs863225140

chr6-135433096-AATCTTCTCTC-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_001134831.2(AHI1):c.2187_2196del(p.Met729IlefsTer36) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHI1 NM_001134831.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.78

Genes affected

AHI1 (HGNC:21575): (Abelson helper integration site 1) This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 6-135433096-AATCTTCTCTC-A is Pathogenic according to our data. Variant chr6-135433096-AATCTTCTCTC-A is described in ClinVar as [Pathogenic]. Clinvar id is 217540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-135433096-AATCTTCTCTC-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.2187_2196del	p.Met729IlefsTer36	frameshift_variant	16/29	ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.2187_2196del	p.Met729IlefsTer36	frameshift_variant	16/29	1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Joubert syndrome 3 Pathogenic:1

Pathogenic, criteria provided, single submitter

research

UW Hindbrain Malformation Research Program, University of Washington

Feb 23, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs863225140; hg19: chr6-135754234;