6-135497750-C-T

Variant names:

• chr6-135497750-C-T
• rs886061114
• ENST00000457866.6:c.-284G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000457866.6(AHI1):​c.-284G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AHI1 ENST00000457866.6 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0790
• Publications: 1 publications found

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]

AHI1-DT (HGNC:32526): (AHI1 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457866.6. 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
	AHI1	NM_001134831.2	MANE Select	c.-369G>A		upstream_gene	N/A	NP_001128303.1	Q8N157-1
	AHI1	NM_001134830.2		c.-222G>A		upstream_gene	N/A	NP_001128302.1	Q8N157-1
	AHI1	NM_001350503.2		c.-478G>A		upstream_gene	N/A	NP_001337432.1	Q8N157-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	ENST00000457866.6	TSL:1	c.-284G>A		5_prime_UTR	Exon 1 of 28	ENSP00000388650.2	Q8N157-1
	AHI1	ENST00000681022.1		c.-2266G>A		5_prime_UTR	Exon 1 of 27	ENSP00000505121.1	Q8N157-1
	AHI1	ENST00000681340.1		c.-455G>A		5_prime_UTR	Exon 1 of 29	ENSP00000505666.1	Q8N157-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 44122 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27404

African (AFR) AF: 0.00 AC: 0 AN: 232

American (AMR) AF: 0.00 AC: 0 AN: 300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 852

East Asian (EAS) AF: 0.00 AC: 0 AN: 114

South Asian (SAS) AF: 0.00 AC: 0 AN: 15522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 116

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 22090

Other (OTH) AF: 0.00 AC: 0 AN: 1578

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Joubert syndrome 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.079
PromoterAI		-0.099	Neutral

Splicing

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

Other links and lift over

dbSNP: rs886061114; hg19: chr6-135818888;