dbSNP rs201271055: CARD19:p.Arg59Ser (chr9-93110592-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032310.5(CARD19):c.175C>A(p.Arg59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R59C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CARD19
NM_032310.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

Publications

2 publications found

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:

ENSG00000223446 (HGNC:):

ENSG00000223446 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30388194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032310.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CARD19	NM_032310.5	MANE Select	c.175C>A	p.Arg59Ser	missense	Exon 3 of 6	NP_115686.3
CARD19	NM_001318011.2		c.175C>A	p.Arg59Ser	missense	Exon 3 of 5	NP_001304940.1
CARD19	NM_001318010.2		c.162-1626C>A		intron	N/A	NP_001304939.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD19	ENST00000375464.7	TSL:1 MANE Select	c.175C>A	p.Arg59Ser	missense	Exon 3 of 6	ENSP00000364613.2	Q96LW7-2
CARD19	ENST00000466409.1	TSL:1	n.175C>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000437237.1	Q96LW7-1
CARD19	ENST00000490488.5	TSL:1	n.217C>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248766

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724780

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.0000224

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25850

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

85908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109386

Other (OTH)

AF:

0.00

AC:

AN:

60216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.00000378

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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0041

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.0

PhyloP100

3.3

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.15

Sift

Benign

0.22

Sift4G

Benign

0.51

Polyphen

0.81

Vest4

0.57

MutPred

0.35

Loss of MoRF binding (P = 0.0221)

MVP

0.18

MPC

0.16

ClinPred

0.47

GERP RS

3.9

gMVP

0.37

Mutation Taster

=55/45

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over