19-12505484-G-C

Variant names:

• chr19-12505484-G-C
• rs10412981
• ENST00000428311.1:c.4-38634C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428311.1(ENSG00000196826):​c.4-38634C>G variant causes a intron 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: ENSG00000196826 ENST00000428311.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 1 publications found

Genes affected

ENSG00000196826 (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTCO2P27		n.12505484G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000196826	ENST00000428311.1	c.4-38634C>G		intron_variant	Intron 1 of 3	2		ENSP00000404127.1
ZNF709	ENST00000455490.1	c.90+8260C>G		intron_variant	Intron 1 of 3	2		ENSP00000398085.1
MTCO2P27	ENST00000420740.1	n.116-180G>C		intron_variant	Intron 1 of 1	6
ZNF709	ENST00000493776.1	n.111+8260C>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.745 AC: 30558 AN: 40992

American (AMR) AF: 0.748 AC: 11318 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2446 AN: 3454

East Asian (EAS) AF: 0.432 AC: 2189 AN: 5064

South Asian (SAS) AF: 0.673 AC: 3184 AN: 4728

European-Finnish (FIN) AF: 0.770 AC: 7977 AN: 10354

Middle Eastern (MID) AF: 0.701 AC: 199 AN: 284

European-Non Finnish (NFE) AF: 0.763 AC: 51486 AN: 67454

Other (OTH) AF: 0.740 AC: 1543 AN: 2084

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
PhyloP100		-1.4

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: rs10412981; hg19: chr19-12616298;