19-12505484-G-C

Position:

• chr19-12505484-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000420740.1(MTCO2P27):​n.116-180G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 150,432 control chromosomes in the GnomAD database, including 41,708 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41708 hom., cov: 26)
• Consequence: MTCO2P27 ENST00000420740.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

MTCO2P27 (HGNC:52156): (MT-CO2 pseudogene 27)

ZNF709 (HGNC:20629): (zinc finger protein 709) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCO2P27	ENST00000420740.1	n.116-180G>C		intron_variant, non_coding_transcript_variant
ZNF709	ENST00000455490.1	c.90+8260C>G		intron_variant		2
ZNF709	ENST00000493776.1	n.111+8260C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 111643 AN: 150314 Hom.: 41676 Cov.: 26

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.738

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.743 AC: 111731 AN: 150432 Hom.: 41708 Cov.: 26 AF XY: 0.739 AC XY: 54269 AN XY: 73452

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.740

Alfa AF: 0.666 Hom.: 1831

Bravo AF: 0.741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.85
DANN	Benign	0.21

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: rs10412981; hg19: chr19-12616298;