chr17-58571925-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031272.5(TEX14):​c.3713G>T​(p.Gly1238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,244 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

TEX14
NM_031272.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.238
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04131168).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TEX14NM_031272.5 linkuse as main transcriptc.3713G>T p.Gly1238Val missense_variant 24/32 ENST00000349033.10 NP_112562.3
TEX14NM_001201457.2 linkuse as main transcriptc.3851G>T p.Gly1284Val missense_variant 25/33 NP_001188386.1
TEX14NM_198393.4 linkuse as main transcriptc.3833G>T p.Gly1278Val missense_variant 25/33 NP_938207.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TEX14ENST00000349033.10 linkuse as main transcriptc.3713G>T p.Gly1238Val missense_variant 24/325 NM_031272.5 ENSP00000268910 A2Q8IWB6-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152126
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00000398
AC:
1
AN:
251296
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.0000616
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJun 07, 2024The c.3833G>T (p.G1278V) alteration is located in exon 25 (coding exon 24) of the TEX14 gene. This alteration results from a G to T substitution at nucleotide position 3833, causing the glycine (G) at amino acid position 1278 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
0.81
DANN
Benign
0.86
DEOGEN2
Benign
0.084
.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.041
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
.;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.012
Sift
Uncertain
0.0020
D;D;T
Sift4G
Benign
0.19
T;T;T
Polyphen
0.65
P;B;B
Vest4
0.093
MutPred
0.20
.;Gain of loop (P = 0.0097);.;
MVP
0.41
MPC
0.066
ClinPred
0.17
T
GERP RS
-1.9
Varity_R
0.075
gMVP
0.12

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: rs571334539; hg19: chr17-56649286; API