8-10826419-G-C

Variant names:

• chr8-10826419-G-C
• rs11776767
• NM_017884.6:c.302-175C>G

Variant summary

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

The NM_017884.6(PINX1):​c.302-175C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,074 control chromosomes in the GnomAD database, including 15,965 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 0.43 (15965 hom., cov: 33)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 79 publications found

Genes affected

PINX1 (HGNC:30046): (PIN2 (TERF1) interacting telomerase inhibitor 1) Enables telomerase RNA binding activity and telomerase inhibitor activity. Involved in several processes, including negative regulation of DNA biosynthetic process; positive regulation of protein localization to nucleolus; and protein localization to organelle. Acts upstream of or within telomere maintenance via telomerase. Located in several cellular components, including chromosomal region; nuclear lumen; and spindle. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017884.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	NM_017884.6	MANE Select	c.302-175C>G		intron	N/A	NP_060354.4
	PINX1	NM_001284356.2		c.302-175C>G		intron	N/A	NP_001271285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	ENST00000314787.8	TSL:1 MANE Select	c.302-175C>G		intron	N/A	ENSP00000318966.3
	PINX1	ENST00000554914.1	TSL:2	c.302-175C>G		intron	N/A	ENSP00000451145.1
	PINX1	ENST00000519088.5	TSL:1	c.302-175C>G		intron	N/A	ENSP00000428853.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65694 AN: 151956 Hom.: 15944 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.432 AC: 65759 AN: 152074 Hom.: 15965 Cov.: 33 AF XY: 0.424 AC XY: 31525 AN XY: 74352

African (AFR) AF: 0.662 AC: 27430 AN: 41456

American (AMR) AF: 0.317 AC: 4851 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3462

East Asian (EAS) AF: 0.221 AC: 1144 AN: 5182

South Asian (SAS) AF: 0.342 AC: 1650 AN: 4826

European-Finnish (FIN) AF: 0.302 AC: 3187 AN: 10556

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24624 AN: 67986

Other (OTH) AF: 0.432 AC: 913 AN: 2112

Alfa AF: 0.345 Hom.: 4874

Bravo AF: 0.442

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.086
DANN	Benign	0.26
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11776767; hg19: chr8-10683929;