Genetic Variant BAALC:p.Arg14Cys (chr8-103140937-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024812.3(BAALC):c.40C>T(p.Arg14Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BAALC
NM_024812.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

0 publications found

Variant links:

Genes affected

BAALC (HGNC:14333): (BAALC binder of MAP3K1 and KLF4) This gene was identified by gene expression studies in patients with acute myeloid leukemia (AML). The gene is conserved among mammals and is not found in lower organisms. Tissues that express this gene develop from the neuroectoderm. Multiple alternatively spliced transcript variants that encode different proteins have been described for this gene; however, some of the transcript variants are found only in AML cell lines. [provided by RefSeq, Jul 2008]

BAALC links:

BAALC-AS2 (HGNC:28595): (BAALC antisense RNA 2)

BAALC-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024812.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAALC	NM_024812.3	MANE Select	c.40C>T	p.Arg14Cys	missense	Exon 1 of 3	NP_079088.1	Q8WXS3-2
BAALC	NM_001364874.1		c.40C>T	p.Arg14Cys	missense	Exon 1 of 4	NP_001351803.1	Q8WXS3-1
BAALC	NM_001024372.2		c.40C>T	p.Arg14Cys	missense	Exon 1 of 2	NP_001019543.1	Q8WXS3-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAALC	ENST00000309982.10	TSL:1 MANE Select	c.40C>T	p.Arg14Cys	missense	Exon 1 of 3	ENSP00000312457.5	Q8WXS3-2
BAALC	ENST00000438105.2	TSL:1	c.40C>T	p.Arg14Cys	missense	Exon 1 of 2	ENSP00000395024.2	Q8WXS3-6
BAALC-AS2	ENST00000436771.4	TSL:1	n.286+317G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1382136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682582

African (AFR)

AF:

0.00

AC:

AN:

28556

American (AMR)

AF:

0.00

AC:

AN:

34328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24162

East Asian (EAS)

AF:

0.00

AC:

AN:

32974

South Asian (SAS)

AF:

0.00

AC:

AN:

77910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073438

Other (OTH)

AF:

0.00

AC:

AN:

57146

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.099

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.95

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.94

PhyloP100

1.3

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.22

Vest4

0.56

MutPred

0.62

Loss of disorder (P = 0.0502)

MVP

0.69

MPC

0.15

ClinPred

0.99

GERP RS

2.1

PromoterAI

0.045

Neutral

(source)

Varity_R

0.48

gMVP

0.12

Mutation Taster

=45/55

disease causing

(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

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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