Genetic Variant TEX14:p.Gly1434Asp (chr17-58557817-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031272.5(TEX14):c.4301G>A(p.Gly1434Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,982 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1434V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TEX14
NM_031272.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.30

Publications

1 publications found

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:

SEPTIN4-AS1 (HGNC:51345): (SEPTIN4 antisense RNA 1)

SEPTIN4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEX14	NM_031272.5	MANE Select	c.4301G>A	p.Gly1434Asp	missense	Exon 31 of 32	NP_112562.3
TEX14	NM_001201457.2		c.4439G>A	p.Gly1480Asp	missense	Exon 32 of 33	NP_001188386.1	Q8IWB6-1
TEX14	NM_198393.4		c.4421G>A	p.Gly1474Asp	missense	Exon 32 of 33	NP_938207.2	Q8IWB6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEX14	ENST00000349033.10	TSL:5 MANE Select	c.4301G>A	p.Gly1434Asp	missense	Exon 31 of 32	ENSP00000268910.8	Q8IWB6-3
TEX14	ENST00000240361.12	TSL:1	c.4439G>A	p.Gly1480Asp	missense	Exon 32 of 33	ENSP00000240361.8	Q8IWB6-1
TEX14	ENST00000389934.7	TSL:1	c.4421G>A	p.Gly1474Asp	missense	Exon 32 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250582

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726232

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.0000224

AC:

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

85978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110916

Other (OTH)

AF:

0.00

AC:

AN:

60320

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.69

PhyloP100

3.3

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.67

MutPred

0.37

Gain of loop (P = 0.0013)

MVP

0.42

MPC

0.34

ClinPred

0.91

GERP RS

4.7

Varity_R

0.50

gMVP

0.051

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over