chr6-89157271-T-G

Position:

• chr6-89157271-T-G

Variant summary

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

The NM_001010853.3(PM20D2):​c.913-1054T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,062 control chromosomes in the GnomAD database, including 5,521 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 0.27 (5521 hom., cov: 32)
• Consequence: PM20D2 NM_001010853.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PM20D2	NM_001010853.3	c.913-1054T>G		intron_variant		ENST00000275072.5	NP_001010853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PM20D2	ENST00000275072.5	c.913-1054T>G		intron_variant		1	NM_001010853.3	ENSP00000275072.4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40530 AN: 151944 Hom.: 5504 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.267 AC: 40589 AN: 152062 Hom.: 5521 Cov.: 32 AF XY: 0.261 AC XY: 19429 AN XY: 74344

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.282

Alfa AF: 0.258 Hom.: 802

Bravo AF: 0.278

Asia WGS AF: 0.231 AC: 803 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.74

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: rs1929635; hg19: chr6-89866990;