rs61732279

chr2-70985275-T-Achr2-70985275-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001115116.2(ANKRD53):c.1568T>A(p.Leu523Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,023,144 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD53 NM_001115116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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]

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1501486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD53	NM_001115116.2	c.1568T>A	p.Leu523Gln	missense_variant	6/6	ENST00000360589.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD53	ENST00000360589.4	c.1568T>A	p.Leu523Gln	missense_variant	6/6	2	NM_001115116.2	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 24 AN: 146336 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000880

Gnomad SAS AF: 0.000471

Gnomad FIN AF: 0.000316

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.000487

GnomAD4 exome AF: 0.000353 AC: 361 AN: 1023144 Hom.: 0 Cov.: 40 AF XY: 0.000347 AC XY: 177 AN XY: 510546

Gnomad4 AFR exome AF: 0.000513

Gnomad4 AMR exome AF: 0.0000318

Gnomad4 ASJ exome AF: 0.000160

Gnomad4 EAS exome AF: 0.0000375

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.0000268

Gnomad4 NFE exome AF: 0.000406

Gnomad4 OTH exome AF: 0.000380

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000164 AC: 24 AN: 146474 Hom.: 0 Cov.: 31 AF XY: 0.000182 AC XY: 13 AN XY: 71356

Gnomad4 AFR AF: 0.0000248

Gnomad4 AMR AF: 0.000202

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000882

Gnomad4 SAS AF: 0.000470

Gnomad4 FIN AF: 0.000316

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.000482

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	17
Dann	Uncertain	0.99
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.62	.;P
Vest4		0.16
MutPred		0.15		.;Gain of disorder (P = 0.0375);
MVP		0.74
MPC		0.62
ClinPred		0.44	T
GERP RS		0.84
Varity_R		0.15
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: rs61732279; hg19: chr2-71212405;