6-158452262-C-A

Position:

• chr6-158452262-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020245.5(TULP4):​c.853C>A​(p.Leu285Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TULP4 NM_020245.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

Genes affected

TULP4 (HGNC:15530): (TUB like protein 4) Predicted to be involved in protein ubiquitination. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TULP4	NM_020245.5	c.853C>A	p.Leu285Met	missense_variant	5/14	ENST00000367097.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP4	ENST00000367097.8	c.853C>A	p.Leu285Met	missense_variant	5/14	1	NM_020245.5	P1
TULP4	ENST00000367094.6	c.853C>A	p.Leu285Met	missense_variant	5/13	1
TULP4	ENST00000616856.1	n.1425C>A		non_coding_transcript_exon_variant	5/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.853C>A (p.L285M) alteration is located in exon 5 (coding exon 5) of the TULP4 gene. This alteration results from a C to A substitution at nucleotide position 853, causing the leucine (L) at amino acid position 285 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.060	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.76	N;N
REVEL	Benign	0.24
Sift	Benign	0.21	T;T
Sift4G	Benign	0.29	T;T
Polyphen		1.0	D;D
Vest4		0.61
MutPred		0.50		Loss of catalytic residue at L285 (P = 0.0135);Loss of catalytic residue at L285 (P = 0.0135);
MVP		0.41
MPC		0.84
ClinPred		0.83	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs940536194; hg19: chr6-158873294;