17-58569261-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PVS1_ModerateBP6BS1BS2

The NM_031272.5(TEX14):c.3818-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 1,613,678 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

TEX14
NM_031272.5 splice_acceptor, intron

Scores

Splicing: ADA: 0.9998

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.0550

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]

TEX14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.015840221 fraction of the gene. Cryptic splice site detected, with MaxEntScore 2.6, offset of 3, new splice context is: tcttttttaaaaactaatAGaag. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BP6

Variant 17-58569261-C-T is Benign according to our data. Variant chr17-58569261-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 746683.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00225 (342/152306) while in subpopulation AFR AF= 0.00664 (276/41566). AF 95% confidence interval is 0.006. There are 2 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TEX14	NM_031272.5 link	c.3818-1G>A	splice_acceptor_variant, intron_variant	Intron 25 of 31	ENST00000349033.10	NP_112562.3	Q8IWB6-3
TEX14	NM_001201457.2 link	c.3956-1G>A	splice_acceptor_variant, intron_variant	Intron 26 of 32		NP_001188386.1	Q8IWB6-1
TEX14	NM_198393.4 link	c.3938-1G>A	splice_acceptor_variant, intron_variant	Intron 26 of 32		NP_938207.2	Q8IWB6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX14	ENST00000349033.10 link	c.3818-1G>A		splice_acceptor_variant, intron_variant	Intron 25 of 31	5	NM_031272.5	ENSP00000268910.8		Q8IWB6-3

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00637

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.000898

AC:

225

AN:

250572

Hom.:

AF XY:

0.000672

AC XY:

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.00679

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.000440

AC:

643

AN:

1461372

Hom.:

Cov.:

AF XY:

0.000398

AC XY:

289

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.00646

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000209

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152306

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00664

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000842

Hom.:

Bravo

AF:

0.00297

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000857

AC:

104

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000475

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Spermatogenic failure 23

Uncertain:1

Jan 08, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.84

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.53

GERP RS

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.71

SpliceAI score (max)

0.87

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -18

DS_AL_spliceai

0.87

Position offset: -1

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