8-103140937-C-T

Variant names:

• chr8-103140937-C-T
• rs866254829
• NM_024812.3:c.40C>T

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAALC	NM_024812.3	c.40C>T	p.Arg14Cys	missense_variant	Exon 1 of 3	ENST00000309982.10	NP_079088.1
BAALC	NM_001364874.1	c.40C>T	p.Arg14Cys	missense_variant	Exon 1 of 4		NP_001351803.1
BAALC	NM_001024372.2	c.40C>T	p.Arg14Cys	missense_variant	Exon 1 of 2		NP_001019543.1
BAALC-AS2	NR_027071.1	n.89+317G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAALC	ENST00000309982.10	c.40C>T	p.Arg14Cys	missense_variant	Exon 1 of 3	1	NM_024812.3	ENSP00000312457.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1382136 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;.;T;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.099
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.60	D;D;D;D;D
MetaSVM	Benign	-0.94	T
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-3.6	D;D;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		0.22	B;.;.;.;.
Vest4		0.56
MutPred		0.62		Loss of disorder (P = 0.0502);Loss of disorder (P = 0.0502);Loss of disorder (P = 0.0502);Loss of disorder (P = 0.0502);Loss of disorder (P = 0.0502);
MVP		0.69
MPC		0.15
ClinPred		0.99	D
GERP RS		2.1
Varity_R		0.48
gMVP		0.12

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

Other links and lift over

dbSNP: rs866254829; hg19: chr8-104153165;