chr12-110013164-T-C

Position:

• chr12-110013164-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033121.2(ANKRD13A):​c.269T>C​(p.Val90Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD13A NM_033121.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18

Genes affected

ANKRD13A (HGNC:21268): (ankyrin repeat domain 13A) Enables ubiquitin-dependent protein binding activity. Involved in negative regulation of protein localization to endosome and negative regulation of receptor internalization. Located in late endosome; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD13A	NM_033121.2	c.269T>C	p.Val90Ala	missense_variant	3/15	ENST00000261739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD13A	ENST00000261739.9	c.269T>C	p.Val90Ala	missense_variant	3/15	1	NM_033121.2	P1
ANKRD13A	ENST00000550404.1	n.528T>C		non_coding_transcript_exon_variant	3/7	1
ANKRD13A	ENST00000553025.5	c.5T>C	p.Val2Ala	missense_variant, NMD_transcript_variant	3/12	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.269T>C (p.V90A) alteration is located in exon 3 (coding exon 3) of the ANKRD13A gene. This alteration results from a T to C substitution at nucleotide position 269, causing the valine (V) at amino acid position 90 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.95	P
Vest4		0.52
MutPred		0.50		Gain of catalytic residue at E88 (P = 0.0295);
MVP		0.66
MPC		0.31
ClinPred		0.95	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.62
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-110450969;