22-37847668-A-T

Position:

• chr22-37847668-A-T

Variant summary

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

The NM_001349853.2(ANKRD54):​c.133+561T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 479,318 control chromosomes in the GnomAD database, including 87,543 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 0.58 (26130 hom., cov: 27)
  • Exomes 𝑓: 0.61 (61413 hom.)
• Consequence: ANKRD54 NM_001349853.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

Genes affected

ANKRD54 (HGNC:25185): (ankyrin repeat domain 54) Predicted to enable protein kinase regulator activity. Predicted to be involved in positive regulation of erythrocyte differentiation; regulation of intracellular signal transduction; and regulation of protein kinase activity. Predicted to act upstream of or within nucleocytoplasmic transport. Predicted to be located in midbody. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MIR659 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD54	NM_001349853.2	c.133+561T>A		intron_variant			NP_001336782.1
ANKRD54	XM_047441138.1	c.133+561T>A		intron_variant			XP_047297094.1
MIR659	NR_030396.1	n.*10T>A		downstream_gene_variant
MIR659	unassigned_transcript_3666	n.*25T>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD54	ENST00000609454.5	c.-28+1269T>A		intron_variant		3		ENSP00000477088.1
MIR659	ENST00000384963.1	n.*10T>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88346 AN: 151296 Hom.: 26121 Cov.: 27

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.581

GnomAD3 exomes AF: 0.607 AC: 121230 AN: 199814 Hom.: 37517 AF XY: 0.607 AC XY: 66777 AN XY: 109934

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.578

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.871

Gnomad SAS exome AF: 0.656

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.592

GnomAD4 exome AF: 0.608 AC: 199206 AN: 327904 Hom.: 61413 Cov.: 0 AF XY: 0.612 AC XY: 115881 AN XY: 189404

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.868

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.597

GnomAD4 genome AF: 0.584 AC: 88393 AN: 151414 Hom.: 26130 Cov.: 27 AF XY: 0.584 AC XY: 43181 AN XY: 73954

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.583

Alfa AF: 0.512 Hom.: 2755

Bravo AF: 0.583

Asia WGS AF: 0.708 AC: 2465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	14
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5750504; hg19: chr22-38243675;