6-89118336-T-G

Variant names:

• chr6-89118336-T-G
• rs423516
• ENST00000842480.1:n.89+164T>G

Variant summary

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

The ENST00000842480.1(ENSG00000309618):​n.89+164T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,032 control chromosomes in the GnomAD database, including 38,652 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 0.71 (38652 hom., cov: 34)
• Consequence: ENSG00000309618 ENST00000842480.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 3 publications found

Genes affected

ENSG00000309618 (HGNC:):

PM20D2 (HGNC:21408): (peptidase M20 domain containing 2) Enables dipeptidase activity and identical protein binding activity. Acts upstream of or within proteolysis and regulation of cellular protein metabolic process. Located in nucleoplasm. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PM20D2	XM_011535481.4	c.-94+20666T>G		intron_variant	Intron 1 of 6		XP_011533783.1
PM20D2	XM_047418220.1	c.-834+20666T>G		intron_variant	Intron 1 of 6		XP_047274176.1
PM20D2	XM_047418221.1	c.-144+20666T>G		intron_variant	Intron 1 of 7		XP_047274177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000309618	ENST00000842480.1	n.89+164T>G		intron_variant	Intron 1 of 3
ENSG00000309618	ENST00000842481.1	n.80+164T>G		intron_variant	Intron 1 of 3
ENSG00000309618	ENST00000842482.1	n.81+164T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108211 AN: 151914 Hom.: 38643 Cov.: 34

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.712 AC: 108261 AN: 152032 Hom.: 38652 Cov.: 34 AF XY: 0.717 AC XY: 53306 AN XY: 74316

African (AFR) AF: 0.706 AC: 29289 AN: 41514

American (AMR) AF: 0.672 AC: 10279 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2288 AN: 3470

East Asian (EAS) AF: 0.798 AC: 4107 AN: 5146

South Asian (SAS) AF: 0.794 AC: 3829 AN: 4824

European-Finnish (FIN) AF: 0.716 AC: 7591 AN: 10602

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48523 AN: 67884

Other (OTH) AF: 0.698 AC: 1468 AN: 2102

Alfa AF: 0.716 Hom.: 5046

Bravo AF: 0.703

Asia WGS AF: 0.766 AC: 2661 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.18
PhyloP100		0.23
PromoterAI		-0.030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs423516; hg19: chr6-89828055;