rs866254829

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-103140937-C-A
• chr8-103140937-C-G
• chr8-103140937-C-T

Variant summary

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

The NM_024812.3(BAALC):​c.40C>A​(p.Arg14Ser) 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. 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: 7.2e-7 (0 hom.)
• Consequence: BAALC NM_024812.3 missense
• Clinical Significance: Not reported in ClinVar
• 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>A	p.Arg14Ser	missense	Exon 1 of 3	NP_079088.1	Q8WXS3-2
	BAALC	NM_001364874.1		c.40C>A	p.Arg14Ser	missense	Exon 1 of 4	NP_001351803.1	Q8WXS3-1
	BAALC	NM_001024372.2		c.40C>A	p.Arg14Ser	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>A	p.Arg14Ser	missense	Exon 1 of 3	ENSP00000312457.5	Q8WXS3-2
	BAALC	ENST00000438105.2	TSL:1	c.40C>A	p.Arg14Ser	missense	Exon 1 of 2	ENSP00000395024.2	Q8WXS3-6
	BAALC-AS2	ENST00000436771.4	TSL:1	n.286+317G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1382136 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682582

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.61	T
PhyloP100		1.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.022	D
Polyphen		0.95	P
Vest4		0.56
MutPred		0.60		Gain of glycosylation at R14 (P = 0.0215)
MVP		0.74
MPC		0.13
ClinPred		0.99	D
GERP RS		2.1
PromoterAI		0.027	Neutral
Varity_R		0.45
gMVP		0.16
Mutation Taster		=38/62	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; COSMIC: COSV107373684;