21-43032912-G-A

Variant names:

• chr21-43032912-G-A
• rs2839629
• NM_004571.5:c.*2811G>A

Variant summary

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

The NM_004571.5(PKNOX1):​c.*2811G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,092 control chromosomes in the GnomAD database, including 18,925 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 0.49 (18925 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PKNOX1 NM_004571.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 14 publications found

Genes affected

PKNOX1 (HGNC:9022): (PBX/knotted 1 homeobox 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in angiogenesis and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within camera-type eye development; hemopoiesis; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. Predicted to be part of chromatin. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX1	NM_004571.5	c.*2811G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000291547.10	NP_004562.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX1	ENST00000291547.10	c.*2811G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_004571.5	ENSP00000291547.4
PKNOX1	ENST00000432907.6	c.*2811G>A		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000402243.2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74838 AN: 151966 Hom.: 18925 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.492 AC: 74879 AN: 152084 Hom.: 18925 Cov.: 32 AF XY: 0.490 AC XY: 36431 AN XY: 74328

African (AFR) AF: 0.612 AC: 25382 AN: 41502

American (AMR) AF: 0.400 AC: 6114 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3369 AN: 5174

South Asian (SAS) AF: 0.472 AC: 2278 AN: 4826

European-Finnish (FIN) AF: 0.435 AC: 4586 AN: 10544

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30232 AN: 67990

Other (OTH) AF: 0.499 AC: 1054 AN: 2112

Alfa AF: 0.453 Hom.: 22769

Bravo AF: 0.498

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.037
DANN	Benign	0.43
PhyloP100		-2.8
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: rs2839629; hg19: chr21-44453022;