5-56100283-C-T

Variant names:

• chr5-56100283-C-T
• rs766207133
• NM_024669.3:c.1745G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024669.3(ANKRD55):​c.1745G>A​(p.Arg582Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R582W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: ANKRD55 NM_024669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87
• Publications: 1 publications found

Genes affected

ANKRD55 (HGNC:25681): (ankyrin repeat domain 55)

ENSG00000249236 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13147971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024669.3. 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
	ANKRD55	NM_024669.3	MANE Select	c.1745G>A	p.Arg582Gln	missense	Exon 12 of 12	NP_078945.2	Q3KP44-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD55	ENST00000341048.9	TSL:2 MANE Select	c.1745G>A	p.Arg582Gln	missense	Exon 12 of 12	ENSP00000342295.4	Q3KP44-1
	ANKRD55	ENST00000434982.2	TSL:1	c.881G>A	p.Arg294Gln	missense	Exon 4 of 4	ENSP00000429421.1	Q3KP44-2
	ANKRD55	ENST00000504958.6	TSL:5	c.1616G>A	p.Arg539Gln	missense	Exon 10 of 10	ENSP00000424230.1	D6RBD3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000482 AC: 12 AN: 249210 AF XY: 0.0000593

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1461858 Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25 AN XY: 727234

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74272

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.000328 AC: 5 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.088
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.9
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Vest4		0.11
MVP		0.44
MPC		0.41
ClinPred		0.20	T
GERP RS		5.0
Varity_R		0.20
gMVP		0.22
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766207133; hg19: chr5-55396110; COSMIC: COSV61947976;