Variant chr19-372670-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016585.5(THEG):c.596G>A(p.Arg199Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

THEG
NM_016585.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

THEG (HGNC:):

THEG links:

SPMAP2 (HGNC:13706): (sperm microtubule associated protein 2) This gene is specifically expressed in the nucleus of haploid male germ cells. The orthologous gene in mice encodes a protein that may play a role in protein assembly through interactions with T-complex protein 1 subunit epsilon. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

SPMAP2 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=0.16937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THEG	NM_016585.5 linkuse as main transcript	c.596G>A	p.Arg199Gln	missense_variant	5/8	ENST00000342640.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPMAP2	ENST00000342640.9 linkuse as main transcript	c.596G>A	p.Arg199Gln	missense_variant	5/8	1	NM_016585.5	A2	Q9P2T0-1
SPMAP2	ENST00000346878.3 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant	4/7	2		P2	Q9P2T0-2
SPMAP2	ENST00000530711.3 linkuse as main transcript	c.86+1629G>A		intron_variant		3
SPMAP2	ENST00000528213.1 linkuse as main transcript	n.403G>A		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251306

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135890

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:

0.0000327

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000207

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 28, 2022

The c.596G>A (p.R199Q) alteration is located in exon 5 (coding exon 5) of the THEG gene. This alteration results from a G to A substitution at nucleotide position 596, causing the arginine (R) at amino acid position 199 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Pathogenic

1.0

Eigen

Benign

0.026

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.11

Sift

Benign

0.081

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.43

MutPred

0.27

.;Gain of ubiquitination at K201 (P = 0.0477);

MVP

0.088

MPC

0.29

ClinPred

0.47

GERP RS

3.3

Varity_R

0.27

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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