17-58572012-G-C

Position:

• chr17-58572012-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031272.5(TEX14):​c.3626C>G​(p.Ser1209Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077231675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX14	NM_031272.5	c.3626C>G	p.Ser1209Cys	missense_variant	24/32	ENST00000349033.10	NP_112562.3
TEX14	NM_001201457.2	c.3764C>G	p.Ser1255Cys	missense_variant	25/33		NP_001188386.1
TEX14	NM_198393.4	c.3746C>G	p.Ser1249Cys	missense_variant	25/33		NP_938207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX14	ENST00000349033.10	c.3626C>G	p.Ser1209Cys	missense_variant	24/32	5	NM_031272.5	ENSP00000268910	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.3746C>G (p.S1249C) alteration is located in exon 25 (coding exon 24) of the TEX14 gene. This alteration results from a C to G substitution at nucleotide position 3746, causing the serine (S) at amino acid position 1249 to be replaced by a cysteine (C). 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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.080	.;T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.039	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.13	B;B;B
Vest4		0.22
MutPred		0.32		.;Loss of disorder (P = 0.0402);.;
MVP		0.30
MPC		0.059
ClinPred		0.18	T
GERP RS		3.2
Varity_R		0.10
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-56649373;