rs553687185

Variant names:

• chr12-51890727-C-G
• NM_182608.4:c.781C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-51890727-C-G
• chr12-51890727-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182608.4(ANKRD33):​c.781C>G​(p.Pro261Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P261S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD33 NM_182608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.24

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3610715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD33	NM_182608.4	c.781C>G	p.Pro261Ala	missense_variant	Exon 5 of 5	ENST00000301190.11	NP_872414.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD33	ENST00000301190.11	c.781C>G	p.Pro261Ala	missense_variant	Exon 5 of 5	2	NM_182608.4	ENSP00000301190.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451616 Hom.: 0 Cov.: 96 AF XY: 0.00 AC XY: 0 AN XY: 722640

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Benign	0.88
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.14
Sift	Benign	0.64	T;T
Sift4G	Benign	0.067	T;T
Vest4		0.42
MutPred		0.46		.;Gain of catalytic residue at P139 (P = 0.0433);
MVP		0.72
MPC		0.49
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-52284511;