Variant chr19-6222542-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000252674.9(MLLT1):c.689C>T(p.Ser230Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000552 in 1,600,890 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

MLLT1
ENST00000252674.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.22

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008472502).

BP6

Variant 19-6222542-G-A is Benign according to our data. Variant chr19-6222542-G-A is described in ClinVar as [Benign]. Clinvar id is 718642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 431 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT1	NM_005934.4 linkuse as main transcript	c.689C>T	p.Ser230Leu	missense_variant	6/12	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.689C>T	p.Ser230Leu	missense_variant	6/12	1	NM_005934.4	ENSP00000252674.6		Q03111

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00946

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000674

AC:

162

AN:

240300

Hom.:

AF XY:

0.000610

AC XY:

AN XY:

131186

show subpopulations

Gnomad AFR exome

AF:

0.00809

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000538

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000312

AC:

452

AN:

1448590

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

203

AN XY:

721100

show subpopulations

Gnomad4 AFR exome

AF:

0.00950

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152300

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00950

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.00323

ESP6500AA

AF:

0.00568

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000792

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

Eigen

Benign

0.12

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0085

MetaSVM

Benign

-0.90

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.85

Vest4

0.22

MVP

0.30

MPC

0.19

ClinPred

0.032

GERP RS

4.8

Varity_R

0.19

gMVP

0.11

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