Variant chr5-40843456-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032587.4(CARD6):c.588T>G(p.Asp196Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

CARD6
NM_032587.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.403

Variant links:

Genes affected

CARD6 (HGNC:16394): (caspase recruitment domain family member 6) This gene encodes a protein that contains a caspase recruitment domain (CARD), an antiparallel six-helical bundle that mediates homotypic protein-protein interactions. The encoded protein is a microtubule-associated protein that has been shown to interact with receptor-interacting protein kinases and positively modulate signal transduction pathways converging on activation of the inducible transcription factor NF-kB. [provided by RefSeq, Jul 2008]

CARD6 links:

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ACMG classification

Classification made for transcript

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=0.08795115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD6	NM_032587.4 linkuse as main transcript	c.588T>G	p.Asp196Glu	missense_variant	2/3	ENST00000254691.10	NP_115976.2	Q9BX69
CARD6	XM_017009989.2 linkuse as main transcript	c.283+1791T>G		intron_variant			XP_016865478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD6	ENST00000254691.10 linkuse as main transcript	c.588T>G	p.Asp196Glu	missense_variant	2/3	1	NM_032587.4	ENSP00000254691.5		Q9BX69
CARD6	ENST00000381677.4 linkuse as main transcript	c.588T>G	p.Asp196Glu	missense_variant	2/3	1		ENSP00000371093.3		A0A0B4J1T5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250196

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Jul 05, 2024

The c.588T>G (p.D196E) alteration is located in exon 2 (coding exon 2) of the CARD6 gene. This alteration results from a T to G substitution at nucleotide position 588, causing the aspartic acid (D) at amino acid position 196 to be replaced by a glutamic acid (E). 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

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0056

T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.040

Sift

Benign

0.089

T;D

Sift4G

Benign

0.29

T;D

Polyphen

0.66

P;.

Vest4

0.11

MutPred

0.29

Gain of loop (P = 0.069);Gain of loop (P = 0.069);

MVP

0.40

MPC

0.035

ClinPred

0.20

GERP RS

-0.42

Varity_R

0.060

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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