6-118558626-TACAC-T

Position:

• chr6-118558626-TACAC-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001042475.3(CEP85L):​c.1020+6899_1020+6902delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (3446 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

Genes affected

CEP85L (HGNC:21638): (centrosomal protein 85 like) The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

PLN (HGNC:9080): (phospholamban) The protein encoded by this gene is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. The encoded protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta-agonists. The encoded protein is a key regulator of cardiac diastolic function. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure, and also familial hypertrophic cardiomyopathy. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 6-118558626-TACAC-T is Benign according to our data. Variant chr6-118558626-TACAC-T is described in ClinVar as [Benign]. Clinvar id is 1252105.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1020+6899_1020+6902delGTGT		intron_variant		ENST00000368491.8	NP_001035940.1
PLN	NM_002667.5	c.-97-167_-97-164delCACA		intron_variant		ENST00000357525.6	NP_002658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.1020+6899_1020+6902delGTGT		intron_variant		1	NM_001042475.3	ENSP00000357477.3
PLN	ENST00000357525.6	c.-97-198_-97-195delACAC		intron_variant		1	NM_002667.5	ENSP00000350132.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 27294 AN: 111282 Hom.: 3443 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.243

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.245 AC: 27304 AN: 111348 Hom.: 3446 Cov.: 0 AF XY: 0.255 AC XY: 13265 AN XY: 52086

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.278

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs371775061; hg19: chr6-118879789;