NM_003322.6:c.1324-730T>C

Variant names:

• chr6-35500882-A-G
• rs1883636
• NM_003322.6:c.1324-730T>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.1324-730T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,224 control chromosomes in the GnomAD database, including 2,124 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 0.16 (2124 hom., cov: 32)
• Consequence: TULP1 NM_003322.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 9 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):

LOC124901309 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TULP1	NM_003322.6	c.1324-730T>C		intron_variant	Intron 13 of 14	ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2	c.1165-730T>C		intron_variant	Intron 12 of 13		NP_001276324.1
LOC124901309	XR_007059561.1	n.75+2675A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11	c.1324-730T>C		intron_variant	Intron 13 of 14	1	NM_003322.6	ENSP00000229771.6

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24108 AN: 152104 Hom.: 2107 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0999

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.159 AC: 24164 AN: 152224 Hom.: 2124 Cov.: 32 AF XY: 0.155 AC XY: 11536 AN XY: 74438

African (AFR) AF: 0.221 AC: 9173 AN: 41506

American (AMR) AF: 0.205 AC: 3144 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 347 AN: 3472

East Asian (EAS) AF: 0.130 AC: 674 AN: 5176

South Asian (SAS) AF: 0.114 AC: 550 AN: 4828

European-Finnish (FIN) AF: 0.0704 AC: 747 AN: 10618

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9046 AN: 68004

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.145 Hom.: 5706

Bravo AF: 0.174

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.88
PhyloP100		-0.39
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: rs1883636; hg19: chr6-35468659;