2-70985275-T-C

Variant names:

• chr2-70985275-T-C
• rs61732279
• NM_001115116.2:c.1568T>C

Variant summary

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

The NM_001115116.2(ANKRD53):​c.1568T>C​(p.Leu523Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,160,058 control chromosomes in the GnomAD database, including 28,624 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.18 (2482 hom., cov: 31)
  • Exomes 𝑓: 0.27 (26142 hom.)
• Consequence: ANKRD53 NM_001115116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050165355).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115116.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD53	NM_001115116.2	MANE Select	c.1568T>C	p.Leu523Pro	missense	Exon 6 of 6	NP_001108588.1	Q8N9V6-1
	ANKRD53	NM_001369683.1		c.1466T>C	p.Leu489Pro	missense	Exon 6 of 6	NP_001356612.1	C9JZ61
	ANKRD53	NM_024933.4		c.*663T>C		3_prime_UTR	Exon 7 of 7	NP_079209.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD53	ENST00000360589.4	TSL:2 MANE Select	c.1568T>C	p.Leu523Pro	missense	Exon 6 of 6	ENSP00000353796.3	Q8N9V6-1
	ANKRD53	ENST00000272421.10	TSL:1	c.*663T>C		3_prime_UTR	Exon 7 of 7	ENSP00000272421.6	Q8N9V6-2
	ENSG00000258881	ENST00000606025.5	TSL:5	c.475+3640A>G		intron	N/A	ENSP00000475641.1	U3KQ87

Frequencies

GnomAD3 genomes AF: 0.184 AC: 26843 AN: 146210 Hom.: 2481 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.167 AC: 25723 AN: 154178 AF XY: 0.166

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.215

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.271 AC: 274328 AN: 1013708 Hom.: 26142 Cov.: 40 AF XY: 0.264 AC XY: 133736 AN XY: 505934

African (AFR) AF: 0.189 AC: 4389 AN: 23182

American (AMR) AF: 0.148 AC: 4654 AN: 31408

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 3961 AN: 18754

East Asian (EAS) AF: 0.271 AC: 7227 AN: 26660

South Asian (SAS) AF: 0.106 AC: 7530 AN: 71352

European-Finnish (FIN) AF: 0.195 AC: 7280 AN: 37268

Middle Eastern (MID) AF: 0.238 AC: 992 AN: 4170

European-Non Finnish (NFE) AF: 0.299 AC: 227091 AN: 759186

Other (OTH) AF: 0.269 AC: 11204 AN: 41728

GnomAD4 genome AF: 0.183 AC: 26854 AN: 146350 Hom.: 2482 Cov.: 31 AF XY: 0.179 AC XY: 12767 AN XY: 71296

African (AFR) AF: 0.141 AC: 5694 AN: 40276

American (AMR) AF: 0.178 AC: 2637 AN: 14802

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 550 AN: 3390

East Asian (EAS) AF: 0.218 AC: 988 AN: 4542

South Asian (SAS) AF: 0.105 AC: 448 AN: 4272

European-Finnish (FIN) AF: 0.149 AC: 1410 AN: 9462

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14246 AN: 66360

Other (OTH) AF: 0.191 AC: 394 AN: 2068

Alfa AF: 0.171 Hom.: 1154

Bravo AF: 0.184

TwinsUK AF: 0.224 AC: 831

ALSPAC AF: 0.225 AC: 866

ESP6500AA AF: 0.135 AC: 187

ESP6500EA AF: 0.200 AC: 637

ExAC AF: 0.118 AC: 3246

Asia WGS AF: 0.135 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.065
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.092
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.12	B
Vest4		0.069
MPC		1.5
ClinPred		0.022	T
GERP RS		0.84
Varity_R		0.14
gMVP		0.40
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: rs61732279; hg19: chr2-71212405; COSMIC: COSV55536270; COSMIC: COSV55536270;