Genetic Variant ANKRD13D:p.Gly73Ser (chr11-67290204-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_207354.3(ANKRD13D):c.217G>A(p.Gly73Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,386,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ANKRD13D
NM_207354.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.71

Publications

0 publications found

Variant links:

Genes affected

ANKRD13D (HGNC:27880): (ankyrin repeat domain 13D) The protein encoded by this gene is a member of the ankyrin repeat domain (ANKRD) 13 family, which currently consists of four proteins containing ubiquitin-interacting motifs. These proteins are integral membrane proteins that bind specifically to Lys-63-linked ubiquitin chains on membrane-bound proteins, targeting those proteins for rapid internalization. [provided by RefSeq, Dec 2016]

ANKRD13D links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD13D	NM_207354.3 link	c.217G>A	p.Gly73Ser	missense_variant	Exon 2 of 15	ENST00000511455.7	NP_997237.2	Q6ZTN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD13D	ENST00000511455.7 link	c.217G>A	p.Gly73Ser	missense_variant	Exon 2 of 15	1	NM_207354.3	ENSP00000427130.2		Q6ZTN6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000692

AC:

AN:

144586

AF XY:

0.0000130

show subpopulations

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:

0.0000170

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

1386782

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

684264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000139

AC:

AN:

1078864

Other (OTH)

AF:

0.00

AC:

AN:

57914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 06, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.217G>A (p.G73S) alteration is located in exon 2 (coding exon 2) of the ANKRD13D gene. This alteration results from a G to A substitution at nucleotide position 217, causing the glycine (G) at amino acid position 73 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.67

PhyloP100

6.7

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.29

Sift

Uncertain

0.028

Sift4G

Benign

0.068

Polyphen

0.97

Vest4

0.61

MutPred

0.61

Gain of relative solvent accessibility (P = 0.09);

MVP

0.38

MPC

0.97

ClinPred

0.97

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.78

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr11-67290204-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over