rs2273000

Variant names:

• chr6-35510691-A-G
• rs2273000
• NM_003322.6:c.499+170T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003322.6(TULP1):​c.499+170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,479,420 control chromosomes in the GnomAD database, including 339,927 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (32135 hom., cov: 31)
  • Exomes 𝑓: 0.68 (307792 hom.)
• Consequence: TULP1 NM_003322.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 3 publications found

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]

TULP1 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 14

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis 15

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000228559 (HGNC:58100):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003322.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TULP1	NM_003322.6	MANE Select	c.499+170T>C		intron	N/A	NP_003313.3
	TULP1	NM_001289395.2		c.340+170T>C		intron	N/A	NP_001276324.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TULP1	ENST00000229771.11	TSL:1 MANE Select	c.499+170T>C		intron	N/A	ENSP00000229771.6
	TULP1	ENST00000322263.8	TSL:1	c.340+170T>C		intron	N/A	ENSP00000319414.4
	TULP1	ENST00000614066.4	TSL:5	c.499+170T>C		intron	N/A	ENSP00000477534.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98389 AN: 151916 Hom.: 32110 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.680 AC: 902986 AN: 1327386 Hom.: 307792 Cov.: 20 AF XY: 0.680 AC XY: 445290 AN XY: 655036

African (AFR) AF: 0.544 AC: 16519 AN: 30382

American (AMR) AF: 0.641 AC: 21835 AN: 34068

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 15016 AN: 22678

East Asian (EAS) AF: 0.696 AC: 25005 AN: 35930

South Asian (SAS) AF: 0.662 AC: 48625 AN: 73472

European-Finnish (FIN) AF: 0.728 AC: 25001 AN: 34332

Middle Eastern (MID) AF: 0.628 AC: 2507 AN: 3992

European-Non Finnish (NFE) AF: 0.686 AC: 711301 AN: 1036926

Other (OTH) AF: 0.669 AC: 37177 AN: 55606

GnomAD4 genome AF: 0.648 AC: 98454 AN: 152034 Hom.: 32135 Cov.: 31 AF XY: 0.651 AC XY: 48376 AN XY: 74302

African (AFR) AF: 0.549 AC: 22761 AN: 41454

American (AMR) AF: 0.642 AC: 9799 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2345 AN: 3468

East Asian (EAS) AF: 0.705 AC: 3642 AN: 5164

South Asian (SAS) AF: 0.650 AC: 3121 AN: 4802

European-Finnish (FIN) AF: 0.734 AC: 7764 AN: 10578

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46841 AN: 67978

Other (OTH) AF: 0.639 AC: 1348 AN: 2110

Alfa AF: 0.672 Hom.: 4284

Bravo AF: 0.637

Asia WGS AF: 0.678 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.048
DANN	Benign	0.38
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2273000; hg19: chr6-35478468; COSMIC: COSV57694280; COSMIC: COSV57694280;