chr6-118481910-AT-A

Variant names:

• chr6-118481910-AT-A
• NM_001042475.3:c.1613delA

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 8P and 1B. PVS1 BS2_Supporting

The NM_001042475.3(CEP85L):​c.1613delA​(p.Asn538IlefsTer8) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000495 in 1,412,844 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: CEP85L NM_001042475.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12

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]

LOC105377971 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BS2: High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1613delA	p.Asn538IlefsTer8	frameshift_variant	Exon 8 of 13	ENST00000368491.8	NP_001035940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.1613delA	p.Asn538IlefsTer8	frameshift_variant	Exon 8 of 13	1	NM_001042475.3	ENSP00000357477.3
CEP85L	ENST00000434604.5	c.1622delA	p.Asn541IlefsTer8	frameshift_variant	Exon 9 of 9	1		ENSP00000392131.1
CEP85L	ENST00000368488.9	c.1622delA	p.Asn541IlefsTer8	frameshift_variant	Exon 9 of 14	5		ENSP00000357474.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000495 AC: 7 AN: 1412844 Hom.: 0 Cov.: 28 AF XY: 0.00000712 AC XY: 5 AN XY: 701938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000262

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000459

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr6-118803073;