6-35498364-G-A

Position:

• chr6-35498364-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_003322.6(TULP1):​c.1592C>T​(p.Ala531Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TULP1 NM_003322.6 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.87

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933
• PP5: Variant 6-35498364-G-A is Pathogenic according to our data. Variant chr6-35498364-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3382015.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TULP1	NM_003322.6	c.1592C>T	p.Ala531Val	missense_variant	15/15	ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2	c.1433C>T	p.Ala478Val	missense_variant	14/14		NP_001276324.1
LOC124901309	XR_007059561.1	n.75+157G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11	c.1592C>T	p.Ala531Val	missense_variant	15/15	1	NM_003322.6	ENSP00000229771.6
TULP1	ENST00000322263.8	c.1433C>T	p.Ala478Val	missense_variant	14/14	1		ENSP00000319414.4
TULP1	ENST00000614066.4	c.1586C>T	p.Ala529Val	missense_variant	14/14	5		ENSP00000477534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa 14;C3151206:Leber congenital amaurosis 15 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Juno Genomics, Hangzhou Juno Genomics, Inc

-

PM2_Supporting+PP3_Moderate+PM3+PP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.88	.;D;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Uncertain	2.8	.;M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.3	D;D;.
REVEL	Pathogenic	0.92
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.75
MutPred		0.84		.;Loss of disorder (P = 0.1337);.;
MVP		0.91
MPC		0.93
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.84
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr6-35466141;