rs2286748

Variant names:

• chr10-102654952-C-A
• rs2286748
• NM_030912.3:c.667-128C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-102654952-C-A
• chr10-102654952-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030912.3(TRIM8):​c.667-128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,140,794 control chromosomes in the GnomAD database, including 54,852 homozygotes. 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: 𝑓 0.30 (6871 hom., cov: 32)
  • Exomes 𝑓: 0.31 (47981 hom.)
• Consequence: TRIM8 NM_030912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105378460 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM8	NM_030912.3	MANE Select	c.667-128C>A		intron	N/A	NP_112174.2	Q9BZR9
	TRIM8	NM_001345950.1		c.571-128C>A		intron	N/A	NP_001332879.1
	TRIM8	NR_144321.1		n.790-128C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM8	ENST00000643721.2	MANE Select	c.667-128C>A		intron	N/A	ENSP00000496301.1	Q9BZR9
	TRIM8	ENST00000302424.13	TSL:1	c.667-128C>A		intron	N/A	ENSP00000302120.6	A0A2U3TZI0
	TRIM8	ENST00000710327.1		c.667-128C>A		intron	N/A	ENSP00000518207.1	Q9BZR9

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45525 AN: 151968 Hom.: 6869 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.308 AC: 304569 AN: 988708 Hom.: 47981 Cov.: 13 AF XY: 0.311 AC XY: 156801 AN XY: 504396

African (AFR) AF: 0.296 AC: 6684 AN: 22612

American (AMR) AF: 0.226 AC: 6667 AN: 29494

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 9680 AN: 21754

East Asian (EAS) AF: 0.296 AC: 10103 AN: 34082

South Asian (SAS) AF: 0.377 AC: 26608 AN: 70524

European-Finnish (FIN) AF: 0.229 AC: 11165 AN: 48718

Middle Eastern (MID) AF: 0.336 AC: 1340 AN: 3990

European-Non Finnish (NFE) AF: 0.306 AC: 218198 AN: 713174

Other (OTH) AF: 0.318 AC: 14124 AN: 44360

GnomAD4 genome AF: 0.300 AC: 45559 AN: 152086 Hom.: 6871 Cov.: 32 AF XY: 0.299 AC XY: 22190 AN XY: 74326

African (AFR) AF: 0.295 AC: 12249 AN: 41480

American (AMR) AF: 0.279 AC: 4268 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3472

East Asian (EAS) AF: 0.316 AC: 1632 AN: 5160

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4818

European-Finnish (FIN) AF: 0.227 AC: 2404 AN: 10574

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20379 AN: 67976

Other (OTH) AF: 0.321 AC: 677 AN: 2112

Alfa AF: 0.282 Hom.: 774

Bravo AF: 0.298

Asia WGS AF: 0.345 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.74
PhyloP100		-0.019
PromoterAI		-0.0038	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2286748;

hg19: chr10-104414709;

COSMIC: COSV56660110;

COSMIC: COSV56660110;