rs536152938

Variant names:

• chr16-88877125-C-A
• rs536152938
• NM_005187.6:c.1813G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88877125-C-A
• chr16-88877125-C-T

Variant summary

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

The NM_005187.6(CBFA2T3):​c.1813G>T​(p.Asp605Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. D605N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CBFA2T3 NM_005187.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 0 publications found

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]

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=0.26334083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBFA2T3	NM_005187.6	c.1813G>T	p.Asp605Tyr	missense_variant	Exon 12 of 12	ENST00000268679.9	NP_005178.4
CBFA2T3	NM_175931.3	c.1555G>T	p.Asp519Tyr	missense_variant	Exon 11 of 11		NP_787127.1
CBFA2T3	XM_005256323.6	c.1738G>T	p.Asp580Tyr	missense_variant	Exon 11 of 11		XP_005256380.1
CBFA2T3	XM_047434826.1	c.*1152G>T		3_prime_UTR_variant	Exon 11 of 11		XP_047290782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBFA2T3	ENST00000268679.9	c.1813G>T	p.Asp605Tyr	missense_variant	Exon 12 of 12	1	NM_005187.6	ENSP00000268679.4
CBFA2T3	ENST00000327483.9	c.1555G>T	p.Asp519Tyr	missense_variant	Exon 11 of 11	1		ENSP00000332122.5
CBFA2T3	ENST00000563856.1	n.780G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
CBFA2T3	ENST00000563920.1	n.918G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396148 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688516

African (AFR) AF: 0.00 AC: 0 AN: 31526

American (AMR) AF: 0.00 AC: 0 AN: 35854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25126

East Asian (EAS) AF: 0.00 AC: 0 AN: 35744

South Asian (SAS) AF: 0.00 AC: 0 AN: 79160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4682

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078584

Other (OTH) AF: 0.00 AC: 0 AN: 57806

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	.;L
PhyloP100		0.16
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.096
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.96	D;D
Vest4		0.19
MutPred		0.31		.;Loss of loop (P = 0.0128);
MVP		0.44
MPC		1.7
ClinPred		0.66	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.28
Mutation Taster		=77/23	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: rs536152938; hg19: chr16-88943533;