chr17-58571979-T-C

Position:

• chr17-58571979-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031272.5(TEX14):​c.3659A>G​(p.Lys1220Arg) 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: 0.0810

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04550454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX14	NM_031272.5	c.3659A>G	p.Lys1220Arg	missense_variant	24/32	ENST00000349033.10
TEX14	NM_001201457.2	c.3797A>G	p.Lys1266Arg	missense_variant	25/33
TEX14	NM_198393.4	c.3779A>G	p.Lys1260Arg	missense_variant	25/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX14	ENST00000349033.10	c.3659A>G	p.Lys1220Arg	missense_variant	24/32	5	NM_031272.5	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Dec 12, 2022

The c.3779A>G (p.K1260R) alteration is located in exon 25 (coding exon 24) of the TEX14 gene. This alteration results from a A to G substitution at nucleotide position 3779, causing the lysine (K) at amino acid position 1260 to be replaced by an arginine (R). 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	0.071
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.6
DANN	Benign	0.93
DEOGEN2	Benign	0.068	.;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.85	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.097
MutPred		0.17		.;Loss of ubiquitination at K1266 (P = 0.0056);.;
MVP		0.34
MPC		0.045
ClinPred		0.060	T
GERP RS		-1.8
Varity_R		0.043
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs2044541958; hg19: chr17-56649340;