rs17511627

Positions:

• chr13-26150190-A-C

Variant summary

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

The ENST00000426792.2(ATP8A2P3):​n.199+618T>G 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 0.185 in 151,692 control chromosomes in the GnomAD database, including 2,711 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 0.19 (2711 hom., cov: 30)
• Consequence: ATP8A2P3 ENST00000426792.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

ATP8A2P3 (HGNC:42641): (ATPase phospholipid transporting 8A2 pseudogene 3)

RNF6 (HGNC:10069): (ring finger protein 6) The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alternatively spliced transcript variants encoding the same protein are observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF6	NM_183045.1	c.409-17739T>G		intron_variant
RNF6	XM_011535178.3	c.409-17739T>G		intron_variant
RNF6	XM_047430498.1	c.409-17739T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8A2P3	ENST00000426792.2	n.199+618T>G		intron_variant, non_coding_transcript_variant
RNF6	ENST00000468480.5	n.769-17739T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28101 AN: 151576 Hom.: 2717 Cov.: 30

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.185 AC: 28096 AN: 151692 Hom.: 2711 Cov.: 30 AF XY: 0.187 AC XY: 13850 AN XY: 74088

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.199

Alfa AF: 0.186 Hom.: 2858

Bravo AF: 0.189

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17511627; hg19: chr13-26724328;