6-35498053-AG-A

Position:

• chr6-35498053-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003322.6(TULP1):​c.*273del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 572,764 control chromosomes in the GnomAD database, including 326 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (252 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (74 hom.)
• Consequence: TULP1 NM_003322.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.811

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-35498053-AG-A is Benign according to our data. Variant chr6-35498053-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 356463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TULP1	NM_003322.6	c.*273del		3_prime_UTR_variant	15/15	ENST00000229771.11
TULP1	NM_001289395.2	c.*273del		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP1	ENST00000229771.11	c.*273del		3_prime_UTR_variant	15/15	1	NM_003322.6	P4
TULP1	ENST00000322263.8	c.*273del		3_prime_UTR_variant	14/14	1		A2
TULP1	ENST00000614066.4	c.*273del		3_prime_UTR_variant	14/14	5		A2

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5194 AN: 151554 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00231

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00286

Gnomad OTH AF: 0.0278

GnomAD4 exome AF: 0.00661 AC: 2785 AN: 421094 Hom.: 74 Cov.: 4 AF XY: 0.00594 AC XY: 1310 AN XY: 220426

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.00377

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00159

Gnomad4 FIN exome AF: 0.000648

Gnomad4 NFE exome AF: 0.00296

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0343 AC: 5209 AN: 151670 Hom.: 252 Cov.: 32 AF XY: 0.0333 AC XY: 2466 AN XY: 74144

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00635

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00210

Gnomad4 FIN AF: 0.000379

Gnomad4 NFE AF: 0.00284

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0231 Hom.: 22

Bravo AF: 0.0391

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Leber congenital amaurosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs112061946; hg19: chr6-35465830;