7-25122022-C-CAAA

Position:

• chr7-25122022-C-CAAA

Variant summary

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

The NM_018947.6(CYCS):​c.*1678_*1679insTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.052 (424 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYCS NM_018947.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

Genes affected

CYCS (HGNC:19986): (cytochrome c, somatic) This gene encodes a small heme protein that functions as a central component of the electron transport chain in mitochondria. The encoded protein associates with the inner membrane of the mitochondrion where it accepts electrons from cytochrome b and transfers them to the cytochrome oxidase complex. This protein is also involved in initiation of apoptosis. Mutations in this gene are associated with autosomal dominant nonsyndromic thrombocytopenia. Numerous processed pseudogenes of this gene are found throughout the human genome.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYCS	NM_018947.6	c.*1678_*1679insTTT		3_prime_UTR_variant	3/3	ENST00000305786.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYCS	ENST00000305786.7	c.*1678_*1679insTTT		3_prime_UTR_variant	3/3	1	NM_018947.6	P1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7587 AN: 146202 Hom.: 426 Cov.: 0

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00334

Gnomad AMR AF: 0.0345

Gnomad ASJ AF: 0.0327

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0850

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0418

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0519 AC: 7590 AN: 146240 Hom.: 424 Cov.: 0 AF XY: 0.0516 AC XY: 3658 AN XY: 70884

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0327

Gnomad4 EAS AF: 0.00120

Gnomad4 SAS AF: 0.0175

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Thrombocytopenia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11427893; hg19: chr7-25161641;