Genetic Variant NM_147195.4:c.2404G>A (chr9-38577992-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_147195.4(ANKRD18A):c.2404G>A(p.Val802Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,564,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ANKRD18A
NM_147195.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.724

Publications

0 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024170458).

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.2404G>A	p.Val802Ile	missense	Exon 13 of 16	NP_671728.2	Q8IVF6-1
	ANKRD18A	NM_001331100.2		c.2590G>A	p.Val864Ile	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.2404G>A	p.Val802Ile	missense	Exon 13 of 16	ENSP00000382610.4	Q8IVF6-1
ANKRD18A	ENST00000602295.5	TSL:1	c.574G>A	p.Val192Ile	missense	Exon 5 of 8	ENSP00000473463.1	R4GN29
ANKRD18A	ENST00000703205.1		c.2590G>A	p.Val864Ile	missense	Exon 15 of 18	ENSP00000515234.1	A0A8V8TQR3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000759

AC:

AN:

171310

AF XY:

0.0000767

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00113

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000297

Gnomad OTH exome

AF:

0.000213

GnomAD4 exome

AF:

0.0000361

AC:

AN:

1412618

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

698328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31874

American (AMR)

AF:

0.00

AC:

AN:

38602

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

25464

East Asian (EAS)

AF:

0.00

AC:

AN:

36948

South Asian (SAS)

AF:

0.00

AC:

AN:

81076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000120

AC:

AN:

1084078

Other (OTH)

AF:

0.000120

AC:

AN:

58438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000528

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

0.086

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.029

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0038

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.36

M_CAP

Benign

0.0027

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PhyloP100

-0.72

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.22

REVEL

Benign

0.031

Sift

Benign

0.19

Sift4G

Benign

0.60

Polyphen

0.0040

Vest4

0.12

MutPred

0.17

Gain of methylation at K806 (P = 0.1272)

MVP

0.030

MPC

0.033

ClinPred

0.021

GERP RS

1.5

Varity_R

0.028

gMVP

0.0072

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over