NM_033121.2:c.674G>A

Variant names:

• chr12-110019268-G-A
• rs745337377
• NM_033121.2:c.674G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_033121.2(ANKRD13A):​c.674G>A​(p.Arg225Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000117 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R225W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: ANKRD13A NM_033121.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3992164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033121.2. 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
	ANKRD13A	NM_033121.2	MANE Select	c.674G>A	p.Arg225Gln	missense	Exon 6 of 15	NP_149112.1	Q8IZ07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD13A	ENST00000261739.9	TSL:1 MANE Select	c.674G>A	p.Arg225Gln	missense	Exon 6 of 15	ENSP00000261739.4	Q8IZ07
	ANKRD13A	ENST00000550404.1	TSL:1	n.933G>A		non_coding_transcript_exon	Exon 6 of 7
	ANKRD13A	ENST00000553025.5	TSL:1	n.410G>A		non_coding_transcript_exon	Exon 6 of 12	ENSP00000474172.1	S4R3D2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251218 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000125 AC: 183 AN: 1461706 Hom.: 0 Cov.: 30 AF XY: 0.000125 AC XY: 91 AN XY: 727150

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000155 AC: 172 AN: 1111888

Other (OTH) AF: 0.000133 AC: 8 AN: 60376

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0068	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		6.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.097
Sift	Benign	0.39	T
Sift4G	Benign	0.60	T
Polyphen		0.98	D
Vest4		0.52
MutPred		0.37		Gain of helix (P = 0.0199)
MVP		0.61
MPC		0.74
ClinPred		0.25	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.52
Mutation Taster		=88/12	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: rs745337377; hg19: chr12-110457073; COSMIC: COSV106084701; COSMIC: COSV106084701;