11-6457014-G-A

Variant names:

• chr11-6457014-G-A
• rs955022236
• NM_033278.4:c.712C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_033278.4(TRIM3):​c.712C>T​(p.Leu238Leu) variant causes a synonymous 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM3 NM_033278.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

Genes affected

TRIM3 (HGNC:10064): (tripartite motif containing 3) The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also called the 'RING-B-box-coiled-coil' (RBCC) subgroup of RING finger proteins. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to cytoplasmic filaments. It is similar to a rat protein which is a specific partner for the tail domain of myosin V, a class of myosins which are involved in the targeted transport of organelles. The rat protein can also interact with alpha-actinin-4. Thus it is suggested that this human protein may play a role in myosin V-mediated cargo transport. Alternatively spliced transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=1.99 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033278.4. 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
	TRIM3	NM_033278.4	MANE Select	c.712C>T	p.Leu238Leu	synonymous	Exon 6 of 12	NP_150594.2
	TRIM3	NM_001248006.2		c.712C>T	p.Leu238Leu	synonymous	Exon 6 of 12	NP_001234935.1	O75382-1
	TRIM3	NM_006458.4		c.712C>T	p.Leu238Leu	synonymous	Exon 7 of 13	NP_006449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	ENST00000345851.8	TSL:1 MANE Select	c.712C>T	p.Leu238Leu	synonymous	Exon 6 of 12	ENSP00000340797.3	O75382-1
	TRIM3	ENST00000359518.7	TSL:5	c.712C>T	p.Leu238Leu	synonymous	Exon 7 of 13	ENSP00000352508.3	O75382-1
	TRIM3	ENST00000525074.5	TSL:2	c.712C>T	p.Leu238Leu	synonymous	Exon 6 of 12	ENSP00000433102.1	O75382-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1437438 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 711752

African (AFR) AF: 0.00 AC: 0 AN: 33186

American (AMR) AF: 0.00 AC: 0 AN: 44404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39232

South Asian (SAS) AF: 0.00 AC: 0 AN: 85760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099234

Other (OTH) AF: 0.00 AC: 0 AN: 59510

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		2.0

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: rs955022236; hg19: chr11-6478244;