2-70984999-A-T

Variant names:

• chr2-70984999-A-T
• rs3796100
• NM_001115116.2:c.1292A>T

Variant summary

Our verdict is Benign. The variant received -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. 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 0.17 (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
• 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=0.005548984).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD53	NM_001115116.2	MANE Select	c.1292A>T	p.His431Leu	missense	Exon 6 of 6	NP_001108588.1
	ANKRD53	NM_001369683.1		c.1190A>T	p.His397Leu	missense	Exon 6 of 6	NP_001356612.1
	ANKRD53	NM_024933.4		c.*387A>T		3_prime_UTR	Exon 7 of 7	NP_079209.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD53	ENST00000360589.4	TSL:2 MANE Select	c.1292A>T	p.His431Leu	missense	Exon 6 of 6	ENSP00000353796.3
	ANKRD53	ENST00000272421.10	TSL:1	c.*387A>T		3_prime_UTR	Exon 7 of 7	ENSP00000272421.6
	ENSG00000258881	ENST00000606025.5	TSL:5	c.475+3916T>A		intron	N/A	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

GnomAD2 exomes AF: 0.165 AC: 25025 AN: 151352 AF XY: 0.165

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 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

African (AFR) AF: 0.103 AC: 3257 AN: 31588

American (AMR) AF: 0.128 AC: 4552 AN: 35638

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 4019 AN: 25088

East Asian (EAS) AF: 0.204 AC: 7289 AN: 35730

South Asian (SAS) AF: 0.0952 AC: 7531 AN: 79142

European-Finnish (FIN) AF: 0.151 AC: 7182 AN: 47604

Middle Eastern (MID) AF: 0.188 AC: 1070 AN: 5692

European-Non Finnish (NFE) AF: 0.212 AC: 228874 AN: 1078466

Other (OTH) AF: 0.191 AC: 11098 AN: 57956

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

African (AFR) AF: 0.106 AC: 4413 AN: 41564

American (AMR) AF: 0.171 AC: 2611 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1036 AN: 5162

South Asian (SAS) AF: 0.0938 AC: 452 AN: 4820

European-Finnish (FIN) AF: 0.142 AC: 1507 AN: 10610

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14357 AN: 67986

Other (OTH) AF: 0.181 AC: 383 AN: 2112

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 v4.9

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
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.083
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.056
Sift	Benign	0.18	T
Sift4G	Benign	0.28	T
Vest4		0.048
MPC		0.48
ClinPred		0.020	T
GERP RS		-1.7
Varity_R		0.076
gMVP		0.40
Mutation Taster		=99/1	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: rs3796100; hg19: chr2-71212129; COSMIC: COSV55538178; COSMIC: COSV55538178;