chr20-18142283-C-T

Variant names:

• chr20-18142283-C-T
• rs2037617604
• NM_001164811.2:c.172C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001164811.2(PET117):​c.172C>T​(p.Gln58*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000722 in 1,384,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PET117 NM_001164811.2 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.14
• Publications: 0 publications found

Genes affected

PET117 (HGNC:40045): (PET117 cytochrome c oxidase chaperone) Predicted to be involved in mitochondrial cytochrome c oxidase assembly. Located in mitochondrion. Implicated in cytochrome-c oxidase deficiency disease. [provided by Alliance of Genome Resources, Apr 2022]

KAT14 (HGNC:15904): (lysine acetyltransferase 14) CSRP2 is a protein containing two LIM domains, which are double zinc finger motifs found in proteins of diverse function. CSRP2 and some related proteins are thought to act as protein adapters, bridging two or more proteins to form a larger protein complex. The protein encoded by this gene binds to one of the LIM domains of CSRP2 and contains an acetyltransferase domain. Although the encoded protein has been detected in the cytoplasm, it is predominantly a nuclear protein. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2011]

KAT14 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-18142283-C-T is Pathogenic according to our data. Variant chr20-18142283-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 981504.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164811.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PET117	NM_001164811.2	MANE Select	c.172C>T	p.Gln58*	stop_gained	Exon 2 of 2	NP_001158283.1	Q6UWS5
	KAT14	NM_001392073.1	MANE Select	c.-378C>T		5_prime_UTR	Exon 2 of 11	NP_001379002.1	A0A075B6H4
	KAT14	NM_001384192.3		c.-378C>T		5_prime_UTR	Exon 2 of 11	NP_001371121.2	Q9H8E8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PET117	ENST00000432901.4	TSL:1 MANE Select	c.172C>T	p.Gln58*	stop_gained	Exon 2 of 2	ENSP00000397881.2	Q6UWS5
	KAT14	ENST00000688188.1	MANE Select	c.-378C>T		5_prime_UTR	Exon 2 of 11	ENSP00000508684.1	A0A075B6H4
	KAT14	ENST00000435364.8	TSL:1	c.-378C>T		5_prime_UTR	Exon 2 of 11	ENSP00000392318.2	Q9H8E8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384882 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 683362

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078856

Other (OTH) AF: 0.0000173 AC: 1 AN: 57914

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Mitochondrial complex IV deficiency, nuclear type 19 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		6.1
Vest4		0.30
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=65/135	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs2037617604; hg19: chr20-18122927;