10-88823286-C-G

Variant summary

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

The NM_144590.3(ANKRD22):c.492G>C(p.Lys164Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ANKRD22 NM_144590.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

Genes affected

ANKRD22 (HGNC:28321): (ankyrin repeat domain 22)

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
ANKRD22	NM_144590.3	c.492G>C	p.Lys164Asn	missense_variant	5/6	ENST00000371930.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD22	ENST00000371930.5	c.492G>C	p.Lys164Asn	missense_variant	5/6	1	NM_144590.3	P1
ANKRD22	ENST00000476963.1	n.230G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

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

Oct 12, 2022

The c.492G>C (p.K164N) alteration is located in exon 5 (coding exon 5) of the ANKRD22 gene. This alteration results from a G to C substitution at nucleotide position 492, causing the lysine (K) at amino acid position 164 to be replaced by an asparagine (N). 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	0.65
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.012
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.24
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.94	P
Vest4		0.49
MutPred		0.46		Loss of ubiquitination at K164 (P = 0.013);
MVP		0.69
MPC		0.58
ClinPred		0.97	D
GERP RS		1.8
Varity_R		0.24
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1843818568; hg19: chr10-90583043;