16-2209190-T-C

Variant names:

• chr16-2209190-T-C
• rs3160
• NM_022372.6:c.*313T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022372.6(MLST8):​c.*313T>C variant causes a 3 prime UTR 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 NM_022372.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 31 publications found

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]

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022372.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLST8	NM_022372.6	MANE Select	c.*313T>C		3_prime_UTR	Exon 9 of 9	NP_071767.3
	MLST8	NM_001352057.2		c.*313T>C		3_prime_UTR	Exon 9 of 9	NP_001338986.1
	MLST8	NM_001199173.3		c.*313T>C		3_prime_UTR	Exon 9 of 9	NP_001186102.1	Q9BVC4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLST8	ENST00000569417.6	TSL:1 MANE Select	c.*313T>C		3_prime_UTR	Exon 9 of 9	ENSP00000456405.1	Q9BVC4-1
	MLST8	ENST00000301724.14	TSL:1	c.*455T>C		3_prime_UTR	Exon 8 of 8	ENSP00000301724.10	A0A0A0MR05
	MLST8	ENST00000568194.5	TSL:1	n.1909T>C		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55071 AN: 151984 Hom.: 12328 Cov.: 33

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.: 6 AF XY: 0.464 AC XY: 129446 AN XY: 279084

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

GnomAD4 genome AF: 0.362 AC: 55075 AN: 152100 Hom.: 12326 Cov.: 33 AF XY: 0.365 AC XY: 27102 AN XY: 74330

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
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)

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

Other links and lift over

dbSNP: rs3160; hg19: chr16-2259191;