chr17-58561554-C-T

Variant summary

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

The NM_031272.5(TEX14):​c.4123G>A​(p.Val1375Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,818 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TEX14
NM_031272.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.231
Variant links:
Genes affected
TEX14 (HGNC:11737): (testis expressed 14, intercellular bridge forming factor) The protein encoded by this gene is necessary for intercellular bridges in germ cells, which are required for spermatogenesis. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

Genome browser will be placed here

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=0.021248698).
BP6
Variant 17-58561554-C-T is Benign according to our data. Variant chr17-58561554-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2246233.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TEX14NM_031272.5 linkuse as main transcriptc.4123G>A p.Val1375Met missense_variant 29/32 ENST00000349033.10 NP_112562.3
TEX14NM_001201457.2 linkuse as main transcriptc.4261G>A p.Val1421Met missense_variant 30/33 NP_001188386.1
TEX14NM_198393.4 linkuse as main transcriptc.4243G>A p.Val1415Met missense_variant 30/33 NP_938207.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TEX14ENST00000349033.10 linkuse as main transcriptc.4123G>A p.Val1375Met missense_variant 29/325 NM_031272.5 ENSP00000268910 A2Q8IWB6-3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251458
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461596
Hom.:
0
Cov.:
29
AF XY:
0.00000825
AC XY:
6
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000724
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsAug 17, 2021This 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
0.066
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
2.4
DANN
Benign
0.55
DEOGEN2
Benign
0.025
.;T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0014
N
LIST_S2
Benign
0.39
T;T;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.021
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
.;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
0.57
N;N;N
REVEL
Benign
0.015
Sift
Benign
0.84
T;T;T
Sift4G
Benign
0.29
T;T;T
Polyphen
0.0010
B;B;B
Vest4
0.14
MutPred
0.098
.;Gain of helix (P = 0.132);.;
MVP
0.15
MPC
0.050
ClinPred
0.014
T
GERP RS
-1.2
Varity_R
0.022
gMVP
0.013

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.

Other links and lift over

dbSNP: rs367928638; hg19: chr17-56638915; COSMIC: COSV53623584; COSMIC: COSV53623584; API