chr17-58569254-G-A

Variant names:

• chr17-58569254-G-A
• rs145643630
• NM_031272.5:c.3824C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BS1_Supporting

The NM_031272.5(TEX14):​c.3824C>T​(p.Ala1275Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000948 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.014891088).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000282 (43/152268) while in subpopulation AMR AF= 0.00196 (30/15288). AF 95% confidence interval is 0.00141. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX14	NM_031272.5	c.3824C>T	p.Ala1275Val	missense_variant	Exon 26 of 32	ENST00000349033.10	NP_112562.3
TEX14	NM_001201457.2	c.3962C>T	p.Ala1321Val	missense_variant	Exon 27 of 33		NP_001188386.1
TEX14	NM_198393.4	c.3944C>T	p.Ala1315Val	missense_variant	Exon 27 of 33		NP_938207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX14	ENST00000349033.10	c.3824C>T	p.Ala1275Val	missense_variant	Exon 26 of 32	5	NM_031272.5	ENSP00000268910.8

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000207 AC: 52 AN: 250764 Hom.: 0 AF XY: 0.000184 AC XY: 25 AN XY: 135570

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.0000753 AC: 110 AN: 1461496 Hom.: 0 Cov.: 30 AF XY: 0.0000646 AC XY: 47 AN XY: 727046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74452

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000374 Hom.: 0

Bravo AF: 0.000310

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000109

EpiControl AF: 0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3944C>T (p.A1315V) alteration is located in exon 27 (coding exon 26) of the TEX14 gene. This alteration results from a C to T substitution at nucleotide position 3944, causing the alanine (A) at amino acid position 1315 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	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	.;T;.
Eigen	Benign	0.033
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.015	T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.5	.;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.030	D;D;D
Sift4G	Benign	0.13	T;T;D
Polyphen		0.81	P;P;P
Vest4		0.30
MVP		0.87
MPC		0.14
ClinPred		0.081	T
GERP RS		3.6
Varity_R		0.070
gMVP		0.069

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs145643630; hg19: chr17-56646615;