chr20-18142268-C-G

Variant names:

• chr20-18142268-C-G
• rs117280420
• NM_001392073.1:c.-393C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001392073.1(KAT14):​c.-393C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000617 in 1,537,076 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (14 hom.)
• Consequence: KAT14 NM_001392073.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.14
• Publications: 5 publications found

Genes affected

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]

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]

PET117 Gene-Disease associations (from GenCC):

• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• mitochondrial complex IV deficiency, nuclear type 19

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005570233).
• BP6: Variant 20-18142268-C-G is Benign according to our data. Variant chr20-18142268-C-G is described in ClinVar as [Benign]. Clinvar id is 726026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000795 (121/152228) while in subpopulation EAS AF = 0.0228 (118/5176). AF 95% confidence interval is 0.0195. There are 1 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT14	NM_001392073.1	c.-393C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	ENST00000688188.1	NP_001379002.1
PET117	NM_001164811.2	c.157C>G	p.Arg53Gly	missense_variant	Exon 2 of 2	ENST00000432901.4	NP_001158283.1
KAT14	NM_001392073.1	c.-393C>G		5_prime_UTR_variant	Exon 2 of 11	ENST00000688188.1	NP_001379002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT14	ENST00000688188.1	c.-393C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11		NM_001392073.1	ENSP00000508684.1
PET117	ENST00000432901.4	c.157C>G	p.Arg53Gly	missense_variant	Exon 2 of 2	1	NM_001164811.2	ENSP00000397881.2
KAT14	ENST00000688188.1	c.-393C>G		5_prime_UTR_variant	Exon 2 of 11		NM_001392073.1	ENSP00000508684.1

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152110 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00166 AC: 236 AN: 141868 AF XY: 0.00148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000237

GnomAD4 exome AF: 0.000598 AC: 828 AN: 1384848 Hom.: 14 Cov.: 30 AF XY: 0.000584 AC XY: 399 AN XY: 683344

African (AFR) AF: 0.0000317 AC: 1 AN: 31592

American (AMR) AF: 0.0000280 AC: 1 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.0215 AC: 767 AN: 35716

South Asian (SAS) AF: 0.000227 AC: 18 AN: 79232

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: 0.00000649 AC: 7 AN: 1078836

Other (OTH) AF: 0.000587 AC: 34 AN: 57914

GnomAD4 genome AF: 0.000795 AC: 121 AN: 152228 Hom.: 1 Cov.: 33 AF XY: 0.000806 AC XY: 60 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0228 AC: 118 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000926

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000469 AC: 10

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.014
Eigen_PC	Benign	0.095
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.65
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Vest4		0.57
MVP		0.28
ClinPred		0.070	T
GERP RS		4.2
Varity_R		0.20
gMVP		0.29
Mutation Taster		=75/25	polymorphism

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: rs117280420; hg19: chr20-18122912;