5-56111622-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_024669.3(ANKRD55):c.1126T>C(p.Ser376Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00674 in 1,579,604 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (63 hom.)
• Consequence: ANKRD55 NM_024669.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.95

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075847805).
• BP6: Variant 5-56111622-A-G is Benign according to our data. Variant chr5-56111622-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 719615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD55	NM_024669.3	c.1126T>C	p.Ser376Pro	missense_variant	10/12	ENST00000341048.9
ANKRD55	XM_047417710.1	c.640T>C	p.Ser214Pro	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD55	ENST00000341048.9	c.1126T>C	p.Ser376Pro	missense_variant	10/12	2	NM_024669.3	P1
ANKRD55	ENST00000434982.2	c.262T>C	p.Ser88Pro	missense_variant	2/4	1
ANKRD55	ENST00000504958.6	c.997T>C	p.Ser333Pro	missense_variant	8/10	5
ANKRD55	ENST00000505970.2	n.809T>C		non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 702 AN: 152096 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00482

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00814

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00438 AC: 945 AN: 215648 Hom.: 5 AF XY: 0.00458 AC XY: 525 AN XY: 114750

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.000876

Gnomad ASJ exome AF: 0.00161

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00146

Gnomad FIN exome AF: 0.00778

Gnomad NFE exome AF: 0.00683

Gnomad OTH exome AF: 0.00431

GnomAD4 exome AF: 0.00697 AC: 9948 AN: 1427390 Hom.: 63 Cov.: 33 AF XY: 0.00685 AC XY: 4843 AN XY: 707386

Gnomad4 AFR exome AF: 0.00109

Gnomad4 AMR exome AF: 0.000881

Gnomad4 ASJ exome AF: 0.00162

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00156

Gnomad4 FIN exome AF: 0.00726

Gnomad4 NFE exome AF: 0.00818

Gnomad4 OTH exome AF: 0.00606

GnomAD4 genome AF: 0.00461 AC: 702 AN: 152214 Hom.: 4 Cov.: 32 AF XY: 0.00430 AC XY: 320 AN XY: 74418

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00482

Gnomad4 NFE AF: 0.00815

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00702 Hom.: 8

Bravo AF: 0.00414

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00837 AC: 72

ExAC AF: 0.00413 AC: 501

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	ANKRD55: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Mar 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.10
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.030	T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.86	D;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.0076	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N;N;D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Vest4		0.21
MVP		0.58
MPC		0.27
ClinPred		0.033	T
GERP RS		5.5
Varity_R		0.58
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

LitVar

Other links and lift over

dbSNP: rs77017041; hg19: chr5-55407449;