Genetic Variant MLLT1:p.Arg473Gln (chr19-6213787-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2

The NM_005934.4(MLLT1):c.1418G>A(p.Arg473Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

MLLT1
NM_005934.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.95

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 -3 ACMG points.

PP5

Variant 19-6213787-C-T is Pathogenic according to our data. Variant chr19-6213787-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 242890.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT1	NM_005934.4 link	c.1418G>A	p.Arg473Gln	missense_variant	Exon 10 of 12	ENST00000252674.9	NP_005925.2	Q03111

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT1	ENST00000252674.9 link	c.1418G>A	p.Arg473Gln	missense_variant	Exon 10 of 12	1	NM_005934.4	ENSP00000252674.6		Q03111
MLLT1	ENST00000585588.1 link	n.453G>A		non_coding_transcript_exon_variant	Exon 4 of 6	3		ENSP00000519594.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250830

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461486

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hypertelorism;C0026827:Hypotonia;C0235946:Cerebral atrophy;C0557874:Global developmental delay;C1854114:Short nose;C1856019:Abnormal cortical gyration;C3887898:Infantile spasms

Pathogenic:1

Jan 10, 2016

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.090

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.55

REVEL

Benign

0.13

Sift

Benign

0.34

Sift4G

Benign

0.59

Polyphen

1.0

Vest4

0.54

MutPred

0.33

Loss of methylation at R473 (P = 0.0238);

MVP

0.53

MPC

0.30

ClinPred

0.74

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