16-2209190-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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	c.*313T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000569417.6	NP_071767.3
BRICD5	NM_182563.4	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	c.*313T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_022372.6	ENSP00000456405.1
BRICD5	ENST00000328540.8	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.: 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

Gnomad4 AFR exome AF: 0.0821

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.427

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

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.357

Alfa AF: 0.447 Hom.: 9568

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
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs3160; hg19: chr16-2259191;