12-56245158-G-T

Variant names:

• chr12-56245158-G-T
• rs199849831
• NM_173595.4:c.2437C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173595.4(ANKRD52):​c.2437C>A​(p.His813Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. H813Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD52 NM_173595.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64
• Publications: 0 publications found

Genes affected

ANKRD52 (HGNC:26614): (ankyrin repeat domain 52)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16968518).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173595.4. 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
	ANKRD52	NM_173595.4	MANE Select	c.2437C>A	p.His813Asn	missense	Exon 22 of 28	NP_775866.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD52	ENST00000267116.8	TSL:1 MANE Select	c.2437C>A	p.His813Asn	missense	Exon 22 of 28	ENSP00000267116.7	Q8NB46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.0033
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.57	N
PhyloP100		4.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.072
Sift	Benign	0.25	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.46		Gain of catalytic residue at H813 (P = 5e-04)
MVP		0.55
MPC		0.92
ClinPred		0.40	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.75
Mutation Taster		=82/18	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: rs199849831; hg19: chr12-56638942;