rs3796100

Positions:

• chr2-70984999-A-T

Variant summary

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

The NM_001115116.2(ANKRD53):​c.1292A>T​(p.His431Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,549,130 control chromosomes in the GnomAD database, including 30,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2429 hom., cov: 33)
  • Exomes 𝑓: 0.20 (28323 hom.)
• Consequence: ANKRD53 NM_001115116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

Genes affected

ANKRD53 (HGNC:25691): (ankyrin repeat domain 53) Involved in mitotic metaphase plate congression; regulation of microtubule cytoskeleton organization; and regulation of mitotic cytokinesis. Located in spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258881 (HGNC:):

TEX261 (HGNC:30712): (testis expressed 261) Predicted to enable COPII receptor activity. Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Predicted to act upstream of or within positive regulation of apoptotic process. Predicted to be located in cytoplasm. Predicted to be integral component of membrane. Predicted to be active in COPII-coated ER to Golgi transport vesicle. Predicted to be integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. [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 (MetaRNN=0.005548984).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD53	NM_001115116.2	c.1292A>T	p.His431Leu	missense_variant	6/6	ENST00000360589.4	NP_001108588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD53	ENST00000360589.4	c.1292A>T	p.His431Leu	missense_variant	6/6	2	NM_001115116.2	ENSP00000353796.3
ENSG00000258881	ENST00000606025.5	c.475+3916T>A		intron_variant		5		ENSP00000475641.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25804 AN: 152108 Hom.: 2428 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.165 AC: 25025 AN: 151352 Hom.: 2315 AF XY: 0.165 AC XY: 13317 AN XY: 80940

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.0963

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.197 AC: 274872 AN: 1396904 Hom.: 28323 Cov.: 95 AF XY: 0.195 AC XY: 134117 AN XY: 688942

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.0952

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.170 AC: 25809 AN: 152226 Hom.: 2429 Cov.: 33 AF XY: 0.166 AC XY: 12338 AN XY: 74414

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.181

Alfa AF: 0.194 Hom.: 978

Bravo AF: 0.172

TwinsUK AF: 0.224 AC: 831

ALSPAC AF: 0.226 AC: 870

ESP6500AA AF: 0.105 AC: 144

ESP6500EA AF: 0.201 AC: 633

ExAC AF: 0.128 AC: 3194

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.8
DANN	Benign	0.75
DEOGEN2	Benign	0.021	.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.46	T;T
MetaRNN	Benign	0.0055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.056
Sift	Benign	0.18	T;T
Sift4G	Benign	0.28	T;T
Vest4		0.048
MPC		0.48
ClinPred		0.020	T
GERP RS		-1.7
Varity_R		0.076
gMVP		0.40

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: rs3796100; hg19: chr2-71212129; COSMIC: COSV55538178; COSMIC: COSV55538178;