chr17-58571925-C-G

Variant names:

• chr17-58571925-C-G
• rs571334539
• NM_031272.5:c.3713G>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.3713G>C​(p.Gly1238Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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=0.059915543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX14	NM_031272.5	c.3713G>C	p.Gly1238Ala	missense_variant	Exon 24 of 32	ENST00000349033.10	NP_112562.3
TEX14	NM_001201457.2	c.3851G>C	p.Gly1284Ala	missense_variant	Exon 25 of 33		NP_001188386.1
TEX14	NM_198393.4	c.3833G>C	p.Gly1278Ala	missense_variant	Exon 25 of 33		NP_938207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX14	ENST00000349033.10	c.3713G>C	p.Gly1238Ala	missense_variant	Exon 24 of 32	5	NM_031272.5	ENSP00000268910.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251296 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135828

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461432 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.39
DANN	Benign	0.84
DEOGEN2	Benign	0.065	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.0060
Sift	Uncertain	0.011	D;D;D
Sift4G	Benign	0.67	T;T;T
Polyphen		0.27	B;B;B
Vest4		0.054
MutPred		0.13		.;Loss of helix (P = 0.0196);.;
MVP		0.37
MPC		0.053
ClinPred		0.044	T
GERP RS		-1.9
Varity_R		0.082
gMVP		0.077

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: rs571334539; hg19: chr17-56649286;