rs13320

Positions:

• chr1-151874041-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053055.5(THEM4):​c.*847G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,082 control chromosomes in the GnomAD database, including 23,949 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 0.55 (23947 hom., cov: 32)
  • Exomes 𝑓: 0.39 (2 hom.)
• Consequence: THEM4 NM_053055.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

THEM4 (HGNC:17947): (thioesterase superfamily member 4) Protein kinase B (PKB) is a major downstream target of receptor tyrosine kinases that signal via phosphatidylinositol 3-kinase. Upon cell stimulation, PKB is translocated to the plasma membrane, where it is phosphorylated in the C-terminal regulatory domain. The protein encoded by this gene negatively regulates PKB activity by inhibiting phosphorylation. Transcription of this gene is commonly downregulated in glioblastomas. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEM4	NM_053055.5	c.*847G>A		3_prime_UTR_variant	6/6	ENST00000368814.8	NP_444283.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEM4	ENST00000368814.8	c.*847G>A		3_prime_UTR_variant	6/6	1	NM_053055.5	ENSP00000357804	P1
THEM4	ENST00000471464.5			downstream_gene_variant		1		ENSP00000431288

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84042 AN: 151944 Hom.: 23936 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.389 AC: 7 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.429

GnomAD4 genome AF: 0.553 AC: 84085 AN: 152064 Hom.: 23947 Cov.: 32 AF XY: 0.554 AC XY: 41183 AN XY: 74334

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.569

Alfa AF: 0.583 Hom.: 35772

Bravo AF: 0.553

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.19

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: rs13320; hg19: chr1-151846517;