Genetic Variant MLST8:n.1909T>C (chr16-2209190-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000568194.5(MLST8):n.1909T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 688,824 control chromosomes in the GnomAD database, including 71,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 12326 hom., cov: 33)

Exomes 𝑓: 0.46 ( 59538 hom. )

Consequence

MLST8
ENST00000568194.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

31 publications found

Variant links:

Genes affected

MLST8 (HGNC:24825): (MTOR associated protein, LST8 homolog) Enables protein serine/threonine kinase activator activity. Involved in TORC1 signaling; positive regulation of TOR signaling; and regulation of actin cytoskeleton organization. Part of TORC1 complex and TORC2 complex. [provided by Alliance of Genome Resources, Apr 2022]

MLST8 links:

BRICD5 (HGNC:28309): (BRICHOS domain containing 5) Predicted to be involved in regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BRICD5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLST8	NM_022372.6 link	c.*313T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000569417.6	NP_071767.3
BRICD5	NM_182563.4 link	c.*172A>G		downstream_gene_variant		ENST00000328540.8	NP_872369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLST8	ENST00000569417.6 link	c.*313T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_022372.6	ENSP00000456405.1
BRICD5	ENST00000328540.8 link	c.*172A>G		downstream_gene_variant		1	NM_182563.4	ENSP00000332389.3

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55071

AN:

151984

Hom.:

12328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0906

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.463

AC:

248270

AN:

536724

Hom.:

59538

Cov.:

AF XY:

0.464

AC XY:

129446

AN XY:

279084

show subpopulations

African (AFR)

AF:

0.0821

AC:

1152

AN:

14030

American (AMR)

AF:

0.483

AC:

9536

AN:

19740

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

5083

AN:

14282

East Asian (EAS)

AF:

0.547

AC:

17310

AN:

31632

South Asian (SAS)

AF:

0.464

AC:

22354

AN:

48160

European-Finnish (FIN)

AF:

0.472

AC:

14484

AN:

30702

Middle Eastern (MID)

AF:

0.364

AC:

787

AN:

2160

European-Non Finnish (NFE)

AF:

0.476

AC:

165162

AN:

346990

Other (OTH)

AF:

0.427

AC:

12402

AN:

29028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7426

14852

22279

29705

37131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1986

3972

5958

7944

9930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.362

AC:

55075

AN:

152100

Hom.:

12326

Cov.:

AF XY:

0.365

AC XY:

27102

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0905

AC:

3756

AN:

41524

American (AMR)

AF:

0.438

AC:

6690

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

1262

AN:

3470

East Asian (EAS)

AF:

0.506

AC:

2621

AN:

5176

South Asian (SAS)

AF:

0.473

AC:

2282

AN:

4828

European-Finnish (FIN)

AF:

0.460

AC:

4862

AN:

10566

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32330

AN:

67932

Other (OTH)

AF:

0.357

AC:

754

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1630

3261

4891

6522

8152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.441

Hom.:

11129

Bravo

AF:

0.345

Asia WGS

AF:

0.475

AC:

1653

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.32

(source)

DANN

Benign

0.33

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(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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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