Variant chr1-151895155-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_053055.5(THEM4):c.139T>G(p.Ser47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

THEM4
NM_053055.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0800

Variant links:

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]

THEM4 links:

ENSG00000285651 (HGNC:):

ENSG00000285651 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023133934).

BP6

Variant 1-151895155-A-C is Benign according to our data. Variant chr1-151895155-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2256400.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEM4	NM_053055.5 linkuse as main transcript	c.139T>G	p.Ser47Ala	missense_variant	2/6	ENST00000368814.8	NP_444283.2	Q5T1C6A8K0C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THEM4	ENST00000368814.8 linkuse as main transcript	c.139T>G	p.Ser47Ala	missense_variant	2/6	1	NM_053055.5	ENSP00000357804.3	Q5T1C6
THEM4	ENST00000471464.5 linkuse as main transcript	n.139T>G		non_coding_transcript_exon_variant	2/7	1		ENSP00000431288.1	F6XC58
THEM4	ENST00000489410.1 linkuse as main transcript	c.139T>G	p.Ser47Ala	missense_variant	2/2	2		ENSP00000433304.1	E9PLJ7
ENSG00000285651	ENST00000648930.1 linkuse as main transcript	n.32-1157A>C		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250976

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461554

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.1

DANN

Benign

0.28

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.92

N;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.046

Sift

Benign

1.0

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.0050

B;.

Vest4

0.19

MutPred

0.22

Gain of catalytic residue at S47 (P = 0.025);Gain of catalytic residue at S47 (P = 0.025);

MVP

0.030

MPC

0.065

ClinPred

0.017

GERP RS

-0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.075

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over