Variant 9-93113021-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032310.5(CARD19):c.466G>A(p.Val156Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,609,382 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 1 hom. )

Consequence

CARD19
NM_032310.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0280

Variant links:

Genes affected

CARD19 (HGNC:28148): (caspase recruitment domain family member 19) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CARD19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030900717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD19	NM_032310.5 linkuse as main transcript	c.466G>A	p.Val156Ile	missense_variant	6/6	ENST00000375464.7	NP_115686.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD19	ENST00000375464.7 linkuse as main transcript	c.466G>A	p.Val156Ile	missense_variant	6/6	1	NM_032310.5	ENSP00000364613	P1	Q96LW7-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000951

AC:

AN:

241910

Hom.:

AF XY:

0.0000991

AC XY:

AN XY:

131186

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000442

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000680

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000940

AC:

137

AN:

1457316

Hom.:

Cov.:

AF XY:

0.0000773

AC XY:

AN XY:

724420

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000586

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000704

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000730

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

AF:

0.000171

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000249

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.466G>A (p.V156I) alteration is located in exon 6 (coding exon 6) of the CARD19 gene. This alteration results from a G to A substitution at nucleotide position 466, causing the valine (V) at amino acid position 156 to be replaced by an isoleucine (I). 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

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.92

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.78

M_CAP

Benign

0.0052

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.35

REVEL

Benign

0.032

Sift

Benign

0.29

Sift4G

Benign

0.30

Polyphen

0.10

Vest4

0.078

MVP

0.040

MPC

0.049

ClinPred

0.051

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.27

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