chr8-103140937-C-G

Variant names:

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

Variant summary

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

The NM_024812.3(BAALC):​c.40C>G​(p.Arg14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,382,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: BAALC NM_024812.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAALC	NM_024812.3	MANE Select	c.40C>G	p.Arg14Gly	missense	Exon 1 of 3	NP_079088.1	Q8WXS3-2
	BAALC	NM_001364874.1		c.40C>G	p.Arg14Gly	missense	Exon 1 of 4	NP_001351803.1	Q8WXS3-1
	BAALC	NM_001024372.2		c.40C>G	p.Arg14Gly	missense	Exon 1 of 2	NP_001019543.1	Q8WXS3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAALC	ENST00000309982.10	TSL:1 MANE Select	c.40C>G	p.Arg14Gly	missense	Exon 1 of 3	ENSP00000312457.5	Q8WXS3-2
	BAALC	ENST00000438105.2	TSL:1	c.40C>G	p.Arg14Gly	missense	Exon 1 of 2	ENSP00000395024.2	Q8WXS3-6
	BAALC-AS2	ENST00000436771.4	TSL:1	n.286+317G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000727 AC: 1 AN: 137584 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000117

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1382136 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 682582

African (AFR) AF: 0.00 AC: 0 AN: 28556

American (AMR) AF: 0.00 AC: 0 AN: 34328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24162

East Asian (EAS) AF: 0.0000303 AC: 1 AN: 32974

South Asian (SAS) AF: 0.00 AC: 0 AN: 77910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073438

Other (OTH) AF: 0.00 AC: 0 AN: 57146

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.46	T
PhyloP100		1.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.022	D
Polyphen		0.97	D
Vest4		0.55
MutPred		0.60		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.75
MPC		0.21
ClinPred		0.81	D
GERP RS		2.1
PromoterAI		0.0040	Neutral
Varity_R		0.49
gMVP		0.15
Mutation Taster		=31/69	disease causing

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

Other links and lift over

dbSNP: rs866254829; hg19: chr8-104153165;