8-103141022-C-T

Variant names:

• chr8-103141022-C-T
• rs1470744383
• NM_024812.3:c.125C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024812.3(BAALC):​c.125C>T​(p.Pro42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000329 in 1,518,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P42R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: BAALC NM_024812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21886784).

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.125C>T	p.Pro42Leu	missense	Exon 1 of 3	NP_079088.1	Q8WXS3-2
	BAALC	NM_001364874.1		c.125C>T	p.Pro42Leu	missense	Exon 1 of 4	NP_001351803.1	Q8WXS3-1
	BAALC	NM_001024372.2		c.125C>T	p.Pro42Leu	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.125C>T	p.Pro42Leu	missense	Exon 1 of 3	ENSP00000312457.5	Q8WXS3-2
	BAALC	ENST00000438105.2	TSL:1	c.125C>T	p.Pro42Leu	missense	Exon 1 of 2	ENSP00000395024.2	Q8WXS3-6
	BAALC-AS2	ENST00000436771.4	TSL:1	n.286+232G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000175 AC: 2 AN: 113990 AF XY: 0.0000159

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000496

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000293 AC: 4 AN: 1366438 Hom.: 0 Cov.: 31 AF XY: 0.00000445 AC XY: 3 AN XY: 674030

African (AFR) AF: 0.00 AC: 0 AN: 27716

American (AMR) AF: 0.00 AC: 0 AN: 32184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23890

East Asian (EAS) AF: 0.00 AC: 0 AN: 31410

South Asian (SAS) AF: 0.00 AC: 0 AN: 76304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5330

European-Non Finnish (NFE) AF: 0.00000375 AC: 4 AN: 1065616

Other (OTH) AF: 0.00 AC: 0 AN: 56396

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74286

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.048
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.025	D
Polyphen		0.52	P
Vest4		0.067
MutPred		0.39		Loss of loop (P = 0.0288)
MVP		0.45
MPC		0.11
ClinPred		0.76	D
GERP RS		3.8
PromoterAI		-0.052	Neutral
Varity_R		0.13
gMVP		0.11
Mutation Taster		=89/11	polymorphism

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: rs1470744383; hg19: chr8-104153250;