Variant chr8-103213011-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024812.3(BAALC):c.253A>G(p.Thr85Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

BAALC
NM_024812.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

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 (HGNC:):

BAALC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20401242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAALC	NM_024812.3 linkuse as main transcript	c.253A>G	p.Thr85Ala	missense_variant	2/3	ENST00000309982.10	NP_079088.1	Q8WXS3-2
BAALC	NM_001364874.1 linkuse as main transcript	c.358A>G	p.Thr120Ala	missense_variant	3/4		NP_001351803.1
BAALC	NM_001024372.2 linkuse as main transcript	c.161-14978A>G		intron_variant			NP_001019543.1	Q8WXS3-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAALC	ENST00000309982.10 linkuse as main transcript	c.253A>G	p.Thr85Ala	missense_variant	2/3	1	NM_024812.3	ENSP00000312457.5		Q8WXS3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2024

The c.253A>G (p.T85A) alteration is located in exon 2 (coding exon 2) of the BAALC gene. This alteration results from a A to G substitution at nucleotide position 253, causing the threonine (T) at amino acid position 85 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.075

.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.094

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.10

Sift

Benign

0.12

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.0040

B;B

Vest4

0.46

MutPred

0.11

.;Loss of phosphorylation at T120 (P = 0.0421);

MVP

0.35

MPC

0.46

ClinPred

0.77

GERP RS

4.3

Varity_R

0.081

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over