Variant 19-6213745-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000252674.9(MLLT1):c.1460A>G(p.Lys487Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000156 in 1,605,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MLLT1
ENST00000252674.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

MLLT1 (HGNC:7134): (MLLT1 super elongation complex subunit) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of protein kinase activity. Located in cytosol; fibrillar center; and nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

MLLT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT1	NM_005934.4 linkuse as main transcript	c.1460A>G	p.Lys487Arg	missense_variant	10/12	ENST00000252674.9	NP_005925.2	Q03111

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT1	ENST00000252674.9 linkuse as main transcript	c.1460A>G	p.Lys487Arg	missense_variant	10/12	1	NM_005934.4	ENSP00000252674.6		Q03111
MLLT1	ENST00000585588.1 linkuse as main transcript	n.495A>G		non_coding_transcript_exon_variant	4/6	3		ENSP00000519594.1

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251150

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135766

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1456208

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

724546

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:

0.0000198

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000670

AC:

AN:

149282

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72804

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000806

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Nov 03, 2023

The c.1460A>G (p.K487R) alteration is located in exon 10 (coding exon 10) of the MLLT1 gene. This alteration results from a A to G substitution at nucleotide position 1460, causing the lysine (K) at amino acid position 487 to be replaced by an arginine (R). 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

0.079

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

M_CAP

Benign

0.070

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.7

REVEL

Benign

0.16

Sift

Uncertain

0.020

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.40

MVP

0.66

MPC

0.25

ClinPred

0.31

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.35

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