2-70979770-C-T

Position:

• chr2-70979770-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001115116.2(ANKRD53):​c.527C>T​(p.Thr176Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ANKRD53 NM_001115116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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]

LOC105374795 (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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD53	NM_001115116.2	c.527C>T	p.Thr176Ile	missense_variant	3/6	ENST00000360589.4
LOC105374795	XR_001739534.2	n.440-3462G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD53	ENST00000360589.4	c.527C>T	p.Thr176Ile	missense_variant	3/6	2	NM_001115116.2	A2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74386

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	1.8	L;.;.;L
MutationTaster	Benign	0.63	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.7	D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.028	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.70
MutPred		0.69		Loss of disorder (P = 0.0505);.;.;Loss of disorder (P = 0.0505);
MVP		0.89
MPC		1.2
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.42
gMVP		0.59

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: rs1231979135; hg19: chr2-71206900;