Variant 16-57984749-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000441824.4(TEPP):c.399G>C(p.Glu133Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,607,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TEPP
ENST00000441824.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0770

Variant links:

Genes affected

SPMIP8 (HGNC:33745): (sperm microtubule inner protein 8) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SPMIP8 links:

TEPP (HGNC:):

TEPP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25328368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPMIP8	NM_199456.3 linkuse as main transcript	c.399G>C	p.Glu133Asp	missense_variant	4/8	ENST00000441824.4	NP_955535.3	Q6URK8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEPP	ENST00000441824.4 linkuse as main transcript	c.399G>C	p.Glu133Asp	missense_variant	4/8	1	NM_199456.3	ENSP00000401917.3	Q6URK8
TEPP	ENST00000290871.10 linkuse as main transcript	c.399G>C	p.Glu133Asp	missense_variant	4/8	1		ENSP00000290871.6	Q6URK8
TEPP	ENST00000569996.5 linkuse as main transcript	n.233G>C		non_coding_transcript_exon_variant	3/8	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

237200

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128530

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000939

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455216

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000451

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.564G>C (p.E188D) alteration is located in exon 4 (coding exon 4) of the TEPP gene. This alteration results from a G to C substitution at nucleotide position 564, causing the glutamic acid (E) at amino acid position 188 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

.;T

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

0.84

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.15

Sift

Benign

0.054

T;T

Sift4G

Benign

0.13

T;T

Polyphen

1.0

D;D

Vest4

0.23

MutPred

0.17

Loss of catalytic residue at W190 (P = 0.0485);Loss of catalytic residue at W190 (P = 0.0485);

MVP

0.38

MPC

0.79

ClinPred

0.80

GERP RS

1.6

Varity_R

0.12

gMVP

0.24

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