3-32818299-C-CCGGCTGCCGGCGGCGGG

Position:

• chr3-32818299-C-CCGGCTGCCGGCGGCGGG

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001039111.3(TRIM71):​c.224_240dupTGCCGGCGGCGGGCGGC​(p.Gly81fs) 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM71 NM_001039111.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.26

Genes affected

TRIM71 (HGNC:32669): (tripartite motif containing 71) The protein encoded by this gene is an E3 ubiquitin-protein ligase that binds with miRNAs and maintains the growth and upkeep of embryonic stem cells. This gene also is involved in the G1-S phase transition of the cell cycle. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Pathogenic. Variant got 12 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 3-32818299-C-CCGGCTGCCGGCGGCGGG is Pathogenic according to our data. Variant chr3-32818299-C-CCGGCTGCCGGCGGCGGG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 996339.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM71	NM_001039111.3	c.224_240dupTGCCGGCGGCGGGCGGC	p.Gly81fs	frameshift_variant	1/4	ENST00000383763.6	NP_001034200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM71	ENST00000383763.6	c.224_240dupTGCCGGCGGCGGGCGGC	p.Gly81fs	frameshift_variant	1/4	1	NM_001039111.3	ENSP00000373272.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-obstructive azoospermia Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Institute of Reproductive Genetics, University of Münster

Mar 01, 2021

PS3, PM2, PP3 -

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: rs1696081301; hg19: chr3-32859791;