7-25122022-C-CA

Position:

• chr7-25122022-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency:
  • Genomes: 𝑓 0.37 (9869 hom., cov: 0)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: CYCS NM_018947.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B: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 Benign. Variant got -10 ACMG points.

• BP6: Variant 7-25122022-C-CA is Benign according to our data. Variant chr7-25122022-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 359924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYCS	NM_018947.6	c.*1678dupT		3_prime_UTR_variant	3/3	ENST00000305786.7	NP_061820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYCS	ENST00000305786	c.*1678dupT		3_prime_UTR_variant	3/3	1	NM_018947.6	ENSP00000307786.2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 53423 AN: 146174 Hom.: 9875 Cov.: 0

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.250 AC: 3 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.365 AC: 53420 AN: 146214 Hom.: 9869 Cov.: 0 AF XY: 0.363 AC XY: 25724 AN XY: 70874

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.369

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Thrombocytopenia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs11427893; hg19: chr7-25161641;