1-151067391-A-C

Position:

• chr1-151067391-A-C

Variant summary

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

The NM_006818.4(MLLT11):​c.167A>C​(p.Asp56Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MLLT11 NM_006818.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.749

Genes affected

MLLT11 (HGNC:16997): (MLLT11 transcription factor 7 cofactor) The gene variously symbolized ALL1, HRX, or MLL located on 11q23 has been demonstrated to be fused with a number of translocation partners in cases of leukemia. t(1;11)(q21;q23) translocations that fused the MLL gene to a gene on chromosomal band 1q21 in 2 infants with acute myelomonocytic leukemia have been demonstrated. The N-terminal portion of the MLL gene is critical for leukemogenesis in translocations involving band 11q23. This gene encodes 90 amino acids. It was found to be highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, this gene was expressed in all leukemic cell lines tested. [provided by RefSeq, Jul 2008]

CDC42SE1 (HGNC:17719): (CDC42 small effector 1) Predicted to enable GTPase inhibitor activity. Predicted to be involved in signal transduction. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

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=0.067276776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT11	NM_006818.4	c.167A>C	p.Asp56Ala	missense_variant	2/2	ENST00000368921.5	NP_006809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT11	ENST00000368921.5	c.167A>C	p.Asp56Ala	missense_variant	2/2	1	NM_006818.4	ENSP00000357917.3
CDC42SE1	ENST00000439374.6	c.-761-57T>G		intron_variant		5		ENSP00000475845.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.167A>C (p.D56A) alteration is located in exon 2 (coding exon 1) of the MLLT11 gene. This alteration results from a A to C substitution at nucleotide position 167, causing the aspartic acid (D) at amino acid position 56 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	0.060
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.038
Sift	Benign	0.29	T
Sift4G	Benign	0.15	T
Polyphen		0.0040	B
Vest4		0.086
MutPred		0.18		Gain of sheet (P = 0.0507);
MVP		0.19
MPC		0.14
ClinPred		0.071	T
GERP RS		3.6
Varity_R		0.073
gMVP		0.077

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: chr1-151039867;