12-56244686-C-T

Variant names:

• chr12-56244686-C-T
• NM_173595.4:c.2688G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173595.4(ANKRD52):​c.2688G>A​(p.Met896Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar 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: 7.91

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD52	NM_173595.4	c.2688G>A	p.Met896Ile	missense_variant	Exon 24 of 28	ENST00000267116.8	NP_775866.2
ANKRD52	XM_017019183.2	c.2685G>A	p.Met895Ile	missense_variant	Exon 23 of 27		XP_016874672.1
ANKRD52	XM_011538197.3	c.2505G>A	p.Met835Ile	missense_variant	Exon 23 of 27		XP_011536499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD52	ENST00000267116.8	c.2688G>A	p.Met896Ile	missense_variant	Exon 24 of 28	1	NM_173595.4	ENSP00000267116.7
ANKRD52	ENST00000548241.1	n.42G>A		non_coding_transcript_exon_variant	Exon 1 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2688G>A (p.M896I) alteration is located in exon 24 (coding exon 24) of the ANKRD52 gene. This alteration results from a G to A substitution at nucleotide position 2688, causing the methionine (M) at amino acid position 896 to be replaced by an isoleucine (I). 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	0.96
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.29
Sift	Benign	0.16	T
Sift4G	Benign	0.081	T
Polyphen		0.88	P
Vest4		0.85
MutPred		0.65		Gain of catalytic residue at R892 (P = 0.0011);
MVP		0.73
MPC		1.8
ClinPred		0.96	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr12-56638470;