rs3850699

Variant names:

• chr10-102654464-A-C
• rs3850699
• NM_030912.3:c.571-189A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-102654464-A-C
• chr10-102654464-A-G
• chr10-102654464-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030912.3(TRIM8):​c.571-189A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM8 NM_030912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• Publications: 0 publications found

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]

TRIM8 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis and neurodevelopmental syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105378460 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030912.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM8	NM_030912.3	MANE Select	c.571-189A>C		intron	N/A	NP_112174.2
	TRIM8	NM_001345950.1		c.571-616A>C		intron	N/A	NP_001332879.1
	TRIM8	NR_144321.1		n.694-189A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM8	ENST00000643721.2	MANE Select	c.571-189A>C		intron	N/A	ENSP00000496301.1
	TRIM8	ENST00000302424.13	TSL:1	c.571-189A>C		intron	N/A	ENSP00000302120.6
	TRIM8	ENST00000710327.1		c.571-189A>C		intron	N/A	ENSP00000518207.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 3

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.48
PhyloP100		-1.0
PromoterAI		0.0093	Neutral

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

Other links and lift over

dbSNP: rs3850699; hg19: chr10-104414221;