rs761305722

Variant names:

• chr14-58427653-C-T
• rs761305722
• ENST00000619416.4:c.-39+16C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-58427653-C-T
• chr14-58427653-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001244189.2(KIAA0586):​c.9+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,383,368 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: KIAA0586 NM_001244189.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

KIAA0586 (HGNC:19960): (KIAA0586) This gene encodes a conserved centrosomal protein that functions in ciliogenesis and responds to hedgehog signaling. Mutations in this gene causes Joubert syndrome 23. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Aug 2016]

TIMM9 (HGNC:11819): (translocase of inner mitochondrial membrane 9) TIMM9 belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.[supplied by OMIM, Apr 2004]

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=-0.36).
• BP6: Variant 14-58427653-C-T is Benign according to our data. Variant chr14-58427653-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1968413.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244189.2. 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
	KIAA0586	NM_001244189.2		c.9+16C>T		intron	N/A	NP_001231118.1	Q9BVV6-3
	KIAA0586	NM_001244190.2		c.-39+16C>T		intron	N/A	NP_001231119.1	Q9BVV6-1
	KIAA0586	NM_001244192.2		c.-57+16C>T		intron	N/A	NP_001231121.1	Q9BVV6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0586	ENST00000619416.4	TSL:1	c.-39+16C>T		intron	N/A	ENSP00000478083.1	Q9BVV6-1
	KIAA0586	ENST00000423743.7	TSL:1	c.-57+16C>T		intron	N/A	ENSP00000399427.3	Q9BVV6-4
	TIMM9	ENST00000922995.1		c.-376G>A		5_prime_UTR	Exon 1 of 5	ENSP00000593054.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000506 AC: 7 AN: 1383368 Hom.: 0 Cov.: 30 AF XY: 0.00000440 AC XY: 3 AN XY: 682580

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000649 AC: 7 AN: 1078870

Other (OTH) AF: 0.00 AC: 0 AN: 57900

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.96
PhyloP100		1.3
PromoterAI		-0.58	Under-expression

Splicing

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

Other links and lift over

dbSNP: rs761305722; hg19: chr14-58894371;