6-35503816-A-T

Variant names:

• chr6-35503816-A-T
• NM_003322.6:c.1145T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_003322.6(TULP1):​c.1145T>A​(p.Phe382Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F382S) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TULP1 NM_003322.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.18

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr6-35503816-A-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TULP1	NM_003322.6	c.1145T>A	p.Phe382Tyr	missense_variant	Exon 12 of 15	ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2	c.986T>A	p.Phe329Tyr	missense_variant	Exon 11 of 14		NP_001276324.1
LOC124901309	XR_007059561.1	n.76-4411A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11	c.1145T>A	p.Phe382Tyr	missense_variant	Exon 12 of 15	1	NM_003322.6	ENSP00000229771.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.40	.;T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.14
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	-0.12	.;N;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.71	N;N;.
REVEL	Uncertain	0.55
Sift	Benign	0.87	T;T;.
Sift4G	Benign	0.78	T;T;T
Polyphen		0.13	B;B;.
Vest4		0.34
MutPred		0.84		.;Gain of phosphorylation at F382 (P = 0.0698);.;
MVP		0.52
MPC		0.47
ClinPred		0.86	D
GERP RS		5.0
Varity_R		0.42
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr6-35471593;