Genetic Variant ANKRD18A:p.Asp827Asn (chr9-38577917-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_147195.4(ANKRD18A):c.2479G>A(p.Asp827Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,597,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ANKRD18A
NM_147195.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.51

Publications

1 publications found

Variant links:

Genes affected

ANKRD18A (HGNC:23643): (ankyrin repeat domain 18A)

ANKRD18A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01719147).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147195.4. 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
	ANKRD18A	NM_147195.4	MANE Select	c.2479G>A	p.Asp827Asn	missense	Exon 13 of 16	NP_671728.2	Q8IVF6-1
	ANKRD18A	NM_001331100.2		c.2665G>A	p.Asp889Asn	missense	Exon 15 of 18	NP_001318029.1	A0A8V8TQR3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD18A	ENST00000399703.6	TSL:1 MANE Select	c.2479G>A	p.Asp827Asn	missense	Exon 13 of 16	ENSP00000382610.4	Q8IVF6-1
ANKRD18A	ENST00000602295.5	TSL:1	c.649G>A	p.Asp217Asn	missense	Exon 5 of 8	ENSP00000473463.1	R4GN29
ANKRD18A	ENST00000703205.1		c.2665G>A	p.Asp889Asn	missense	Exon 15 of 18	ENSP00000515234.1	A0A8V8TQR3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000190

AC:

AN:

226630

AF XY:

0.000203

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.000108

AC:

156

AN:

1445642

Hom.:

Cov.:

AF XY:

0.0000989

AC XY:

AN XY:

718186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32668

American (AMR)

AF:

0.0000690

AC:

AN:

43462

Ashkenazi Jewish (ASJ)

AF:

0.00293

AC:

AN:

25924

East Asian (EAS)

AF:

0.00

AC:

AN:

39050

South Asian (SAS)

AF:

0.0000357

AC:

AN:

84050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52486

Middle Eastern (MID)

AF:

0.00115

AC:

AN:

4342

European-Non Finnish (NFE)

AF:

0.0000471

AC:

AN:

1104092

Other (OTH)

AF:

0.000285

AC:

AN:

59568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000192

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.52

M_CAP

Benign

0.0037

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

3.5

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.1

REVEL

Benign

0.12

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

0.94

Vest4

0.17

MVP

0.055

MPC

0.20

ClinPred

0.11

GERP RS

1.5

Varity_R

0.065

gMVP

0.020

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over