rs1555568575

chr17-58587937-CTGCCGGTGGCT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_031272.5(TEX14):c.2650_2660del(p.Ser884GlyfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEX14 NM_031272.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.25

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-58587937-CTGCCGGTGGCT-C is Pathogenic according to our data. Variant chr17-58587937-CTGCCGGTGGCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 440758.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-58587937-CTGCCGGTGGCT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX14	NM_031272.5	c.2650_2660del	p.Ser884GlyfsTer23	frameshift_variant	16/32	ENST00000349033.10
TEX14	NM_001201457.2	c.2668_2678del	p.Ser890GlyfsTer23	frameshift_variant	16/33
TEX14	NM_198393.4	c.2650_2660del	p.Ser884GlyfsTer23	frameshift_variant	16/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX14	ENST00000349033.10	c.2650_2660del	p.Ser884GlyfsTer23	frameshift_variant	16/32	5	NM_031272.5	A2
TEX14	ENST00000240361.12	c.2668_2678del	p.Ser890GlyfsTer23	frameshift_variant	16/33	1		A2
TEX14	ENST00000389934.7	c.2650_2660del	p.Ser884GlyfsTer23	frameshift_variant	16/33	1		P4
TEX14	ENST00000582740.1	c.*2488_*2498del		3_prime_UTR_variant, NMD_transcript_variant	16/32	1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 23 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555568575; hg19: chr17-56665298;