6-35498368-T-TGGCGAA

Position:

• chr6-35498368-T-TGGCGAA

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_003322.6(TULP1):​c.1582_1587dupTTCGCC​(p.Ala529_Ile530insPheAla) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TULP1 NM_003322.6 conservative_inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.58

Genes affected

TULP1 (HGNC:12423): (TUB like protein 1) This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15. [provided by RefSeq, Nov 2016]

LOC124901309 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003322.6.
• PP5: Variant 6-35498368-T-TGGCGAA is Pathogenic according to our data. Variant chr6-35498368-T-TGGCGAA is described in ClinVar as [Pathogenic]. Clinvar id is 30263.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TULP1	NM_003322.6	c.1582_1587dupTTCGCC	p.Ala529_Ile530insPheAla	conservative_inframe_insertion	15/15	ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2	c.1423_1428dupTTCGCC	p.Ala476_Ile477insPheAla	conservative_inframe_insertion	14/14		NP_001276324.1
LOC124901309	XR_007059561.1	n.75+165_75+170dupGAAGGC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11	c.1582_1587dupTTCGCC	p.Ala529_Ile530insPheAla	conservative_inframe_insertion	15/15	1	NM_003322.6	ENSP00000229771.6
TULP1	ENST00000322263.8	c.1423_1428dupTTCGCC	p.Ala476_Ile477insPheAla	conservative_inframe_insertion	14/14	1		ENSP00000319414.4
TULP1	ENST00000614066.4	c.1576_1581dupTTCGCC	p.Ala527_Ile528insPheAla	conservative_inframe_insertion	14/14	5		ENSP00000477534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Leber congenital amaurosis 15 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35466145;