Genetic Variant MLLT6:p.Gly207Arg (chr17-38711913-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005937.4(MLLT6):c.619G>A(p.Gly207Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MLLT6
NM_005937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22189867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT6	NM_005937.4 link	c.619G>A	p.Gly207Arg	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.619G>A	p.Gly207Arg	missense_variant	Exon 7 of 20	1	NM_005937.4	ENSP00000479910.1	P55198
MLLT6	ENST00000620609.4 link	c.619G>A	p.Gly207Arg	missense_variant	Exon 7 of 9	1		ENSP00000482928.1	Q6P2C6
MLLT6	ENST00000620482.4 link	n.632G>A		non_coding_transcript_exon_variant	Exon 7 of 9	1
MLLT6	ENST00000618652.1 link	n.358G>A		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456508

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724476

African (AFR)

AF:

0.00

AC:

AN:

33354

American (AMR)

AF:

0.00

AC:

AN:

44106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39384

South Asian (SAS)

AF:

0.00

AC:

AN:

85614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109214

Other (OTH)

AF:

0.00

AC:

AN:

60056

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.619G>A (p.G207R) alteration is located in exon 7 (coding exon 7) of the MLLT6 gene. This alteration results from a G to A substitution at nucleotide position 619, causing the glycine (G) at amino acid position 207 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

0.31

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.036

Eigen_PC

Benign

0.033

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.85

T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.69

.;N

PhyloP100

3.1

PrimateAI

Uncertain

0.52

Sift4G

Benign

0.10

T;T

Polyphen

0.97

D;P

Vest4

0.45

MutPred

0.35

Gain of methylation at G207 (P = 0.0024);Gain of methylation at G207 (P = 0.0024);

MVP

0.14

ClinPred

0.50

GERP RS

3.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.3

Varity_R

0.069

gMVP

0.43

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over