6-35498053-AG-A

Variant names:

• chr6-35498053-AG-A
• rs112061946
• NM_003322.6:c.*273delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003322.6(TULP1):​c.*273delC 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
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P
• 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

LINC03135 (HGNC:58100):

LOC124901309 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TULP1	NM_003322.6	MANE Select	c.*273delC		3_prime_UTR	Exon 15 of 15	NP_003313.3
	TULP1	NM_001289395.2		c.*273delC		3_prime_UTR	Exon 14 of 14	NP_001276324.1	O00294-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TULP1	ENST00000229771.11	TSL:1 MANE Select	c.*273delC		3_prime_UTR	Exon 15 of 15	ENSP00000229771.6	O00294-1
	TULP1	ENST00000322263.8	TSL:1	c.*273delC		3_prime_UTR	Exon 14 of 14	ENSP00000319414.4	O00294-2
	TULP1	ENST00000614066.4	TSL:5	c.*273delC		3_prime_UTR	Exon 14 of 14	ENSP00000477534.1	A0A087WT25

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

African (AFR) AF: 0.113 AC: 1347 AN: 11910

American (AMR) AF: 0.0131 AC: 231 AN: 17636

Ashkenazi Jewish (ASJ) AF: 0.00377 AC: 49 AN: 13014

East Asian (EAS) AF: 0.00 AC: 0 AN: 29422

South Asian (SAS) AF: 0.00159 AC: 65 AN: 40782

European-Finnish (FIN) AF: 0.000648 AC: 18 AN: 27782

Middle Eastern (MID) AF: 0.0152 AC: 28 AN: 1848

European-Non Finnish (NFE) AF: 0.00296 AC: 751 AN: 254138

Other (OTH) AF: 0.0121 AC: 296 AN: 24562

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

African (AFR) AF: 0.113 AC: 4669 AN: 41280

American (AMR) AF: 0.0162 AC: 247 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 22 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00210 AC: 10 AN: 4768

European-Finnish (FIN) AF: 0.000379 AC: 4 AN: 10542

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 67892

Other (OTH) AF: 0.0275 AC: 58 AN: 2106

Alfa AF: 0.0231 Hom.: 22

Bravo AF: 0.0391

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis (1)
-	-	1	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81
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: rs112061946; hg19: chr6-35465830;