rs147663052

Variant names:

• chr2-70981956-C-G
• rs147663052
• NM_001115116.2:c.638C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-70981956-C-G
• chr2-70981956-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001115116.2(ANKRD53):​c.638C>G​(p.Thr213Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T213M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANKRD53 NM_001115116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.964

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.638C>G	p.Thr213Arg	missense	Exon 4 of 6	NP_001108588.1	Q8N9V6-1
	ANKRD53	NM_001369683.1		c.536C>G	p.Thr179Arg	missense	Exon 4 of 6	NP_001356612.1	C9JZ61
	ANKRD53	NM_024933.4		c.638C>G	p.Thr213Arg	missense	Exon 4 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.638C>G	p.Thr213Arg	missense	Exon 4 of 6	ENSP00000353796.3	Q8N9V6-1
	ANKRD53	ENST00000272421.10	TSL:1	c.638C>G	p.Thr213Arg	missense	Exon 4 of 7	ENSP00000272421.6	Q8N9V6-2
	ENSG00000258881	ENST00000606025.5	TSL:5	c.475+6959G>C		intron	N/A	ENSP00000475641.1	U3KQ87

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443354 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716958

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 42172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25250

East Asian (EAS) AF: 0.00 AC: 0 AN: 38826

South Asian (SAS) AF: 0.00 AC: 0 AN: 83764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102494

Other (OTH) AF: 0.00 AC: 0 AN: 59500

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.2
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Pathogenic	0.76
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.82		Gain of methylation at T213 (P = 0.0549)
MVP		0.89
MPC		1.2
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.93
gMVP		0.81
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs147663052; hg19: chr2-71209086;