rs201101361

Variant names:

• chr16-88881339-C-A
• NM_005187.6:c.1354G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88881339-C-A
• chr16-88881339-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005187.6(CBFA2T3):​c.1354G>T​(p.Ala452Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. A452T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CBFA2T3 NM_005187.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

Genes affected

CBFA2T3 (HGNC:1537): (CBFA2/RUNX1 partner transcriptional co-repressor 3) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(16;21)(q24;q22) translocation is one of the less common karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. This gene is also a putative breast tumor suppressor. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

ENSG00000259881 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03136486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBFA2T3	NM_005187.6	c.1354G>T	p.Ala452Ser	missense_variant	Exon 9 of 12	ENST00000268679.9	NP_005178.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBFA2T3	ENST00000268679.9	c.1354G>T	p.Ala452Ser	missense_variant	Exon 9 of 12	1	NM_005187.6	ENSP00000268679.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429054 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 708458

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.0050
DANN	Benign	0.52
DEOGEN2	Benign	0.049	.;T;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.26	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.67	.;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.15	N;N;N
REVEL	Benign	0.043
Sift	Benign	0.97	T;T;T
Sift4G	Benign	0.85	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.17
MutPred		0.25		.;Gain of phosphorylation at A452 (P = 0.0039);.;
MVP		0.22
MPC		0.060
ClinPred		0.034	T
GERP RS		-10
Varity_R		0.034
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88947747;