Variant 9-38575615-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_147195.4(ANKRD18A):c.2825C>T(p.Thr942Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,551,488 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.013 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 40 hom. )

Consequence

ANKRD18A
NM_147195.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

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

ANKRD18A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003243506).

BP6

Variant 9-38575615-G-A is Benign according to our data. Variant chr9-38575615-G-A is described in ClinVar as [Benign]. Clinvar id is 780803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1992/152322) while in subpopulation AFR AF= 0.0408 (1697/41556). AF 95% confidence interval is 0.0392. There are 35 homozygotes in gnomad4. There are 891 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD18A	NM_147195.4 linkuse as main transcript	c.2825C>T	p.Thr942Ile	missense_variant	15/16	ENST00000399703.6	NP_671728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD18A	ENST00000399703.6 linkuse as main transcript	c.2825C>T	p.Thr942Ile	missense_variant	15/16	1	NM_147195.4	ENSP00000382610	A2	Q8IVF6-1

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1984

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00446

AC:

702

AN:

157364

Hom.:

AF XY:

0.00375

AC XY:

312

AN XY:

83148

show subpopulations

Gnomad AFR exome

AF:

0.0398

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00863

Gnomad SAS exome

AF:

0.00220

Gnomad FIN exome

AF:

0.0000592

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00428

GnomAD4 exome

AF:

0.00344

AC:

4818

AN:

1399166

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

2358

AN XY:

690078

show subpopulations

Gnomad4 AFR exome

AF:

0.0405

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.00333

Gnomad4 SAS exome

AF:

0.00256

Gnomad4 FIN exome

AF:

0.000101

Gnomad4 NFE exome

AF:

0.00255

Gnomad4 OTH exome

AF:

0.00519

GnomAD4 genome

AF:

0.0131

AC:

1992

AN:

152322

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

891

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00868

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00687

Hom.:

Bravo

AF:

0.0143

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00415

AC:

ExAC

AF:

0.00575

AC:

143

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.0020

DANN

Benign

0.30

DEOGEN2

Benign

0.0078

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

.;D

REVEL

Benign

0.14

Sift

Benign

0.044

.;D

Sift4G

Benign

0.22

T;T

Polyphen

0.011

.;B

Vest4

0.082

MVP

0.055

MPC

0.028

ClinPred

0.0086

GERP RS

-0.89

Varity_R

0.077

gMVP

0.018

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over