10-88823335-T-G

Variant names:

• chr10-88823335-T-G
• rs2304804
• NM_144590.3:c.443A>C
• ANKRD22 p.Gln148Pro

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144590.3(ANKRD22):​c.443A>C​(p.Gln148Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 1,613,796 control chromosomes in the GnomAD database, including 2,894 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.086 (1056 hom., cov: 30)
  • Exomes 𝑓: 0.040 (1838 hom.)
• Consequence: ANKRD22 NM_144590.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 9 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016914606).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144590.3. 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
	ANKRD22	NM_144590.3	MANE Select	c.443A>C	p.Gln148Pro	missense	Exon 5 of 6	NP_653191.2	Q5VYY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD22	ENST00000371930.5	TSL:1 MANE Select	c.443A>C	p.Gln148Pro	missense	Exon 5 of 6	ENSP00000360998.4	Q5VYY1
	ANKRD22	ENST00000892167.1		c.326A>C	p.Gln109Pro	missense	Exon 4 of 5	ENSP00000562226.1
	ANKRD22	ENST00000476963.1	TSL:2	n.181A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13050 AN: 152078 Hom.: 1055 Cov.: 30

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0741

GnomAD2 exomes AF: 0.0444 AC: 11177 AN: 251472 AF XY: 0.0410

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0394

Gnomad ASJ exome AF: 0.0568

Gnomad EAS exome AF: 0.00343

Gnomad FIN exome AF: 0.0191

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0495

GnomAD4 exome AF: 0.0400 AC: 58406 AN: 1461600 Hom.: 1838 Cov.: 31 AF XY: 0.0392 AC XY: 28488 AN XY: 727122

African (AFR) AF: 0.217 AC: 7259 AN: 33454

American (AMR) AF: 0.0425 AC: 1901 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 1454 AN: 26132

East Asian (EAS) AF: 0.0111 AC: 442 AN: 39700

South Asian (SAS) AF: 0.0252 AC: 2174 AN: 86256

European-Finnish (FIN) AF: 0.0193 AC: 1033 AN: 53418

Middle Eastern (MID) AF: 0.0864 AC: 498 AN: 5766

European-Non Finnish (NFE) AF: 0.0364 AC: 40520 AN: 1111766

Other (OTH) AF: 0.0518 AC: 3125 AN: 60386

GnomAD4 genome AF: 0.0859 AC: 13073 AN: 152196 Hom.: 1056 Cov.: 30 AF XY: 0.0828 AC XY: 6163 AN XY: 74408

African (AFR) AF: 0.215 AC: 8905 AN: 41488

American (AMR) AF: 0.0526 AC: 805 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3472

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5178

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4828

European-Finnish (FIN) AF: 0.0194 AC: 206 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0372 AC: 2528 AN: 67994

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0528 Hom.: 1623

Bravo AF: 0.0934

Asia WGS AF: 0.0300 AC: 105 AN: 3478

EpiCase AF: 0.0416

EpiControl AF: 0.0405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.10	N
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.055
Sift	Benign	0.18	T
Sift4G	Benign	0.32	T
Varity_R		0.45
gMVP		0.66
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2304804;

hg19: chr10-90583092;