rs61732279

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-70985275-T-A
• chr2-70985275-T-C
• chr2-70985275-T-G

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• 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: Likely_benign. The variant received -2 ACMG points.

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

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>A	p.Leu523Gln	missense	Exon 6 of 6	NP_001108588.1	Q8N9V6-1
	ANKRD53	NM_001369683.1		c.1466T>A	p.Leu489Gln	missense	Exon 6 of 6	NP_001356612.1	C9JZ61
	ANKRD53	NM_024933.4		c.*663T>A		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>A	p.Leu523Gln	missense	Exon 6 of 6	ENSP00000353796.3	Q8N9V6-1
	ANKRD53	ENST00000272421.10	TSL:1	c.*663T>A		3_prime_UTR	Exon 7 of 7	ENSP00000272421.6	Q8N9V6-2
	ENSG00000258881	ENST00000606025.5	TSL:5	c.475+3640A>T		intron	N/A	ENSP00000475641.1	U3KQ87

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 24 AN: 146336 Hom.: 0 Cov.: 31

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000513 AC: 12 AN: 23370

American (AMR) AF: 0.0000318 AC: 1 AN: 31408

Ashkenazi Jewish (ASJ) AF: 0.000160 AC: 3 AN: 18804

East Asian (EAS) AF: 0.0000375 AC: 1 AN: 26680

South Asian (SAS) AF: 0.000182 AC: 13 AN: 71568

European-Finnish (FIN) AF: 0.0000268 AC: 1 AN: 37304

Middle Eastern (MID) AF: 0.000475 AC: 2 AN: 4214

European-Non Finnish (NFE) AF: 0.000406 AC: 312 AN: 767746

Other (OTH) AF: 0.000380 AC: 16 AN: 42050

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000248 AC: 1 AN: 40342

American (AMR) AF: 0.000202 AC: 3 AN: 14826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.000882 AC: 4 AN: 4534

South Asian (SAS) AF: 0.000470 AC: 2 AN: 4254

European-Finnish (FIN) AF: 0.000316 AC: 3 AN: 9502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000151 AC: 10 AN: 66376

Other (OTH) AF: 0.000482 AC: 1 AN: 2074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.065
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	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
Mutation Taster		=100/0	polymorphism

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;