rs78556816

Positions:

• chr2-68158894-C-T

Variant summary

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

The NM_020143.4(PNO1):​c.357+365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 152,230 control chromosomes in the GnomAD database, including 134 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 0.023 (134 hom., cov: 32)
• Consequence: PNO1 NM_020143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

PNO1 (HGNC:32790): (partner of NOB1 homolog) Enables RNA binding activity. Located in nucleolus and nucleoplasm. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNO1	NM_020143.4	c.357+365C>T		intron_variant		ENST00000263657.7
PNO1	NM_001329916.2	c.357+365C>T		intron_variant
PNO1	NM_001329917.2	c.357+365C>T		intron_variant
PNO1	NR_138146.2	n.404+365C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNO1	ENST00000263657.7	c.357+365C>T		intron_variant		1	NM_020143.4	P1
PNO1	ENST00000430742.1	c.357+365C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3469 AN: 152112 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0230 AC: 3494 AN: 152230 Hom.: 134 Cov.: 32 AF XY: 0.0221 AC XY: 1648 AN XY: 74430

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0171 Hom.: 19

Bravo AF: 0.0260

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.62

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: rs78556816; hg19: chr2-68386026;