chr10-102644784-ACC-TCT

Position:

• chr10-102644784-ACC-TCT

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_030912.3(TRIM8):​c.167_169delinsTCT​(p.Asn56_Gln57delinsIleTer) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM8 NM_030912.3 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22

Genes affected

TRIM8 (HGNC:15579): (tripartite motif containing 8) This gene encodes a member of the tripartite motif (TRIM) protein family. Based on similarities to other proteins, the encoded protein is suspected to be an E3 ubiquitin-protein ligase. Regulation of this gene may be altered in some cancers. Mutations resulting in a truncated protein product have been observed in early-onset epileptic encephalopathy (EOEE). [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Pathogenic. Variant got 10 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM8	NM_030912.3	c.167_169delinsTCT	p.Asn56_Gln57delinsIleTer	stop_gained	1/6	ENST00000643721.2
TRIM8	NM_001345950.1	c.167_169delinsTCT	p.Asn56_Gln57delinsIleTer	stop_gained	1/5
TRIM8	NR_144321.1	n.290_292delinsTCT		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM8	ENST00000643721.2	c.167_169delinsTCT	p.Asn56_Gln57delinsIleTer	stop_gained	1/6		NM_030912.3	P1
TRIM8	ENST00000302424.12	c.167_169delinsTCT	p.Asn56_Gln57delinsIleTer	stop_gained	1/5	1
TRIM8	ENST00000710327.1	c.167_169delinsTCT	p.Asn56_Gln57delinsIleTer	stop_gained	1/6			P1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Focal segmental glomerulosclerosis and neurodevelopmental syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Sep 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr10-104404541;