6-158479796-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_020245.5(TULP4):c.1072T>C(p.Leu358=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 1,614,142 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (20 hom.)
• Consequence: TULP4 NM_020245.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.56

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 6-158479796-T-C is Benign according to our data. Variant chr6-158479796-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2657087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.56 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TULP4	NM_020245.5	c.1072T>C	p.Leu358=	synonymous_variant	7/14	ENST00000367097.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP4	ENST00000367097.8	c.1072T>C	p.Leu358=	synonymous_variant	7/14	1	NM_020245.5	P1
TULP4	ENST00000367094.6	c.1072T>C	p.Leu358=	synonymous_variant	7/13	1
TULP4	ENST00000616856.1	n.1644T>C		non_coding_transcript_exon_variant	7/8	2
TULP4	ENST00000613390.1	c.127T>C	p.Leu43=	synonymous_variant, NMD_transcript_variant	2/6	5

Frequencies

GnomAD3 genomes AF: 0.000683 AC: 104 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00147 AC: 369 AN: 250840 Hom.: 1 AF XY: 0.00193 AC XY: 262 AN XY: 135618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00794

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000495

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000885 AC: 1294 AN: 1461804 Hom.: 20 Cov.: 31 AF XY: 0.00120 AC XY: 875 AN XY: 727186

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.00467

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00883

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000232

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.000676 AC: 103 AN: 152338 Hom.: 0 Cov.: 33 AF XY: 0.000846 AC XY: 63 AN XY: 74496

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000654 Hom.: 0

Bravo AF: 0.000548

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

TULP4: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	10
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs142094605; hg19: chr6-158900828;