12-51890623-C-G

Variant names:

• chr12-51890623-C-G
• rs763937048
• NM_182608.4:c.677C>G

Variant summary

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

The NM_182608.4(ANKRD33):​c.677C>G​(p.Thr226Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T226M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD33 NM_182608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

Genes affected

ANKRD33 (HGNC:13788): (ankyrin repeat domain 33) Predicted to be involved in negative regulation of transcription by RNA polymerase II and negative regulation of transcription regulatory region DNA binding activity. Predicted to act upstream of or within skeletal muscle cell differentiation. Predicted to be located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182608.4. 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
	ANKRD33	NM_182608.4	MANE Select	c.677C>G	p.Thr226Arg	missense	Exon 5 of 5	NP_872414.3
	ANKRD33	NM_001304459.2		c.365C>G	p.Thr122Arg	missense	Exon 6 of 6	NP_001291388.1
	ANKRD33	NM_001130015.2		c.302C>G	p.Thr101Arg	missense	Exon 5 of 6	NP_001123487.1	Q7Z3H0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD33	ENST00000301190.11	TSL:2 MANE Select	c.677C>G	p.Thr226Arg	missense	Exon 5 of 5	ENSP00000301190.6	Q7Z3H0-2
	ANKRD33	ENST00000340970.8	TSL:1	c.302C>G	p.Thr101Arg	missense	Exon 5 of 6	ENSP00000344690.4	Q7Z3H0-1
	ANKRD33	ENST00000547119.1	TSL:1	n.689C>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247056 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458068 Hom.: 0 Cov.: 87 AF XY: 0.00 AC XY: 0 AN XY: 725578

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.58	D
PhyloP100		1.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.54
Sift	Benign	0.083	T
Sift4G	Uncertain	0.0020	D
Vest4		0.47
MutPred		0.64		Gain of catalytic residue at L103 (P = 0.001)
MVP		0.94
MPC		0.63
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.49
gMVP		0.94
Mutation Taster		=76/24	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: rs763937048; hg19: chr12-52284407;