Genetic Variant NM_031272.5:c.4138C>T (chr17-58561539-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_031272.5(TEX14):c.4138C>T(p.Leu1380Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,613,162 control chromosomes in the GnomAD database, including 37 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 32 hom. )

Consequence

TEX14
NM_031272.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.69

Publications

3 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006213367).

BP6

Variant 17-58561539-G-A is Benign according to our data. Variant chr17-58561539-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 779460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00574 (874/152322) while in subpopulation AFR AF = 0.00924 (384/41578). AF 95% confidence interval is 0.00847. There are 5 homozygotes in GnomAd4. There are 438 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 874 AD gene.

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.4138C>T	p.Leu1380Phe	missense	Exon 29 of 32	NP_112562.3
TEX14	NM_001201457.2		c.4276C>T	p.Leu1426Phe	missense	Exon 30 of 33	NP_001188386.1	Q8IWB6-1
TEX14	NM_198393.4		c.4258C>T	p.Leu1420Phe	missense	Exon 30 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.4138C>T	p.Leu1380Phe	missense	Exon 29 of 32	ENSP00000268910.8	Q8IWB6-3
TEX14	ENST00000240361.12	TSL:1	c.4276C>T	p.Leu1426Phe	missense	Exon 30 of 33	ENSP00000240361.8	Q8IWB6-1
TEX14	ENST00000389934.7	TSL:1	c.4258C>T	p.Leu1420Phe	missense	Exon 30 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

872

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00921

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00567

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00420

AC:

1055

AN:

251428

AF XY:

0.00425

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00548

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00535

AC:

7817

AN:

1460840

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

3879

AN XY:

726826

show subpopulations

African (AFR)

AF:

0.00885

AC:

296

AN:

33452

American (AMR)

AF:

0.00380

AC:

170

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00417

AC:

109

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00154

AC:

133

AN:

86226

European-Finnish (FIN)

AF:

0.000524

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00604

AC:

6708

AN:

1111084

Other (OTH)

AF:

0.00545

AC:

329

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

344

687

1031

1374

1718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00574

AC:

874

AN:

152322

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

438

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00924

AC:

384

AN:

41578

American (AMR)

AF:

0.00470

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00104

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00567

AC:

386

AN:

68018

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

148

198

247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00580

Hom.:

Bravo

AF:

0.00591

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00437

AC:

531

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00622

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

Eigen

Benign

0.15

Eigen_PC

Benign

0.014

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

2.7

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.060

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.29

MVP

0.45

MPC

0.28

ClinPred

0.024

GERP RS

4.1

Varity_R

0.070

gMVP

0.024

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over