12-51888274-C-G

Variant names:

• chr12-51888274-C-G
• rs778218317
• NM_182608.4:c.88C>G

Variant summary

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

The NM_182608.4(ANKRD33):​c.88C>G​(p.Arg30Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,459,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (1 hom.)
• Consequence: ANKRD33 NM_182608.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.23
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08068806).

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.88C>G	p.Arg30Gly	missense	Exon 1 of 5	NP_872414.3
	ANKRD33	NM_001304459.2		c.-314C>G		5_prime_UTR	Exon 1 of 6	NP_001291388.1
	ANKRD33	NM_001130015.2		c.-314C>G		5_prime_UTR	Exon 1 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.88C>G	p.Arg30Gly	missense	Exon 1 of 5	ENSP00000301190.6	Q7Z3H0-2
	ANKRD33	ENST00000340970.8	TSL:1	c.-314C>G		5_prime_UTR	Exon 1 of 6	ENSP00000344690.4	Q7Z3H0-1
	ANKRD33	ENST00000547119.1	TSL:1	n.11C>G		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250888 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1459978 Hom.: 1 Cov.: 35 AF XY: 0.0000124 AC XY: 9 AN XY: 726360

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39492

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53024

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111078

Other (OTH) AF: 0.0000996 AC: 6 AN: 60252

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.091
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.6
DANN	Benign	0.74
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
PhyloP100		-3.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MutPred		0.52		Loss of sheet (P = 0.0181)
MVP		0.048
MPC		0.33
ClinPred		0.53	D
GERP RS		-1.2
PromoterAI		0.017	Neutral
Varity_R		0.075
gMVP		0.43
Mutation Taster		=100/0	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: rs778218317; hg19: chr12-52282058;