9-93111915-A-C

Variant names:

• chr9-93111915-A-C
• NM_032310.5:c.341A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032310.5(CARD19):​c.341A>C​(p.Gln114Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: CARD19 NM_032310.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08167085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD19	NM_032310.5	c.341A>C	p.Gln114Pro	missense_variant	Exon 4 of 6	ENST00000375464.7	NP_115686.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD19	ENST00000375464.7	c.341A>C	p.Gln114Pro	missense_variant	Exon 4 of 6	1	NM_032310.5	ENSP00000364613.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341A>C (p.Q114P) alteration is located in exon 4 (coding exon 4) of the CARD19 gene. This alteration results from a A to C substitution at nucleotide position 341, causing the glutamine (Q) at amino acid position 114 to be replaced by a proline (P). 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	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.66
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.068
Sift	Benign	0.21	T
Sift4G	Benign	0.18	T
Polyphen		0.34	B
Vest4		0.39
MutPred		0.20		Gain of glycosylation at S111 (P = 0.0627);
MVP		0.076
MPC		0.083
ClinPred		0.62	D
GERP RS		0.86
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-95874197;