rs750069868

Variant names:

• chr6-135447113-A-C
• rs750069868
• NM_001134831.2:c.1674T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-135447113-A-C
• chr6-135447113-A-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001134831.2(AHI1):​c.1674T>G​(p.Gly558Gly) variant causes a synonymous 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHI1 NM_001134831.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.69
• Publications: 0 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 Gene-Disease associations (from GenCC):

• Joubert syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, ClinGen, Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.143).
• BP6: Variant 6-135447113-A-C is Benign according to our data. Variant chr6-135447113-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 461741.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.69 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134831.2. 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.1674T>G	p.Gly558Gly	synonymous	Exon 13 of 29	NP_001128303.1	Q8N157-1
	AHI1	NM_001134830.2		c.1674T>G	p.Gly558Gly	synonymous	Exon 11 of 27	NP_001128302.1	Q8N157-1
	AHI1	NM_001350503.2		c.1674T>G	p.Gly558Gly	synonymous	Exon 13 of 29	NP_001337432.1	Q8N157-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	ENST00000265602.11	TSL:1 MANE Select	c.1674T>G	p.Gly558Gly	synonymous	Exon 13 of 29	ENSP00000265602.6	Q8N157-1
	AHI1	ENST00000367800.8	TSL:1	c.1674T>G	p.Gly558Gly	synonymous	Exon 11 of 27	ENSP00000356774.4	Q8N157-1
	AHI1	ENST00000457866.6	TSL:1	c.1674T>G	p.Gly558Gly	synonymous	Exon 12 of 28	ENSP00000388650.2	Q8N157-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs750069868; hg19: chr6-135768251;