Genetic Variant MLLT6:p.Gly192Arg (chr17-38711868-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005937.4(MLLT6):c.574G>C(p.Gly192Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,585,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

MLLT6
NM_005937.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.707

Publications

2 publications found

Variant links:

Genes affected

MLLT6 (HGNC:7138): (MLLT6, PHD finger containing) Enables histone binding activity and nucleosome binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including negative regulation of histone H3-K79 methylation; renal potassium excretion; and renal sodium excretion. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MLLT6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24156186).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT6	NM_005937.4 link	c.574G>C	p.Gly192Arg	missense_variant	Exon 7 of 20	ENST00000621332.5	NP_005928.2	P55198

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MLLT6	ENST00000621332.5 link	c.574G>C	p.Gly192Arg	missense_variant	Exon 7 of 20	1	NM_005937.4	ENSP00000479910.1	P55198
MLLT6	ENST00000620609.4 link	c.574G>C	p.Gly192Arg	missense_variant	Exon 7 of 9	1		ENSP00000482928.1	Q6P2C6
MLLT6	ENST00000620482.4 link	n.587G>C		non_coding_transcript_exon_variant	Exon 7 of 9	1
MLLT6	ENST00000618652.1 link	n.313G>C		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000914

AC:

AN:

218928

AF XY:

0.0000169

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000558

AC:

AN:

1432838

Hom.:

Cov.:

AF XY:

0.00000563

AC XY:

AN XY:

710836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32572

American (AMR)

AF:

0.00

AC:

AN:

40384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24526

East Asian (EAS)

AF:

0.00

AC:

AN:

38804

South Asian (SAS)

AF:

0.0000122

AC:

AN:

82028

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.00000547

AC:

AN:

1097710

Other (OTH)

AF:

0.00

AC:

AN:

59100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.77

T;T

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.24

T;T

MetaSVM

Pathogenic

1.2

MutationAssessor

Benign

1.1

.;L

PhyloP100

0.71

PrimateAI

Uncertain

0.60

Sift4G

Benign

0.14

T;T

Polyphen

0.91

P;P

Vest4

0.38

MutPred

0.32

Gain of MoRF binding (P = 0.004);Gain of MoRF binding (P = 0.004);

MVP

0.13

ClinPred

0.14

GERP RS

3.2

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.084

gMVP

0.44

Mutation Taster

=100/0

polymorphism

(source)

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

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17-38711868-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over