17-58561539-G-A

Position:

• chr17-58561539-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (32 hom.)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.69

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]

ACMG classification

Verdict is Benign. Variant got -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]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX14	NM_031272.5	c.4138C>T	p.Leu1380Phe	missense_variant	29/32	ENST00000349033.10	NP_112562.3
TEX14	NM_001201457.2	c.4276C>T	p.Leu1426Phe	missense_variant	30/33		NP_001188386.1
TEX14	NM_198393.4	c.4258C>T	p.Leu1420Phe	missense_variant	30/33		NP_938207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX14	ENST00000349033.10	c.4138C>T	p.Leu1380Phe	missense_variant	29/32	5	NM_031272.5	ENSP00000268910	A2

Frequencies

GnomAD3 genomes AF: 0.00573 AC: 872 AN: 152204 Hom.: 5 Cov.: 32

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

GnomAD3 exomes AF: 0.00420 AC: 1055 AN: 251428 Hom.: 2 AF XY: 0.00425 AC XY: 577 AN XY: 135880

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 SAS exome AF: 0.00170

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.: 32 Cov.: 29 AF XY: 0.00534 AC XY: 3879 AN XY: 726826

Gnomad4 AFR exome AF: 0.00885

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.00417

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00604

Gnomad4 OTH exome AF: 0.00545

GnomAD4 genome AF: 0.00574 AC: 874 AN: 152322 Hom.: 5 Cov.: 32 AF XY: 0.00588 AC XY: 438 AN XY: 74490

Gnomad4 AFR AF: 0.00924

Gnomad4 AMR AF: 0.00470

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00567

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00584 Hom.: 3

Bravo AF: 0.00591

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.00628 AC: 54

ExAC AF: 0.00437 AC: 531

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00654

EpiControl AF: 0.00622

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	.;T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.62	T;T;T
MetaRNN	Benign	0.0062	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.060	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.29
MVP		0.45
MPC		0.28
ClinPred		0.024	T
GERP RS		4.1
Varity_R		0.070
gMVP		0.024

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

LitVar

Other links and lift over

dbSNP: rs114562657; hg19: chr17-56638900;