20-18142351-A-G

Variant names:

• chr20-18142351-A-G
• NM_001164811.2:c.240A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001164811.2(PET117):​c.240A>G​(p.Lys80Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PET117 NM_001164811.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 20-18142351-A-G is Benign according to our data. Variant chr20-18142351-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3389618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1 with no splicing effect.

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.240A>G	p.Lys80Lys	synonymous	Exon 2 of 2	NP_001158283.1	Q6UWS5
	KAT14	NM_001392073.1	MANE Select	c.-310A>G		5_prime_UTR	Exon 2 of 11	NP_001379002.1	A0A075B6H4
	KAT14	NM_001384192.3		c.-310A>G		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.240A>G	p.Lys80Lys	synonymous	Exon 2 of 2	ENSP00000397881.2	Q6UWS5
	KAT14	ENST00000688188.1	MANE Select	c.-310A>G		5_prime_UTR	Exon 2 of 11	ENSP00000508684.1	A0A075B6H4
	KAT14	ENST00000435364.8	TSL:1	c.-310A>G		5_prime_UTR	Exon 2 of 11	ENSP00000392318.2	Q9H8E8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.5
DANN	Benign	0.89
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

hg19: chr20-18122995;