11-6457796-G-T

Variant names:

• chr11-6457796-G-T
• NM_033278.4:c.415C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033278.4(TRIM3):​c.415C>A​(p.Arg139Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM3 NM_033278.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.66

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35744506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM3	NM_033278.4	c.415C>A	p.Arg139Ser	missense_variant	Exon 4 of 12	ENST00000345851.8	NP_150594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM3	ENST00000345851.8	c.415C>A	p.Arg139Ser	missense_variant	Exon 4 of 12	1	NM_033278.4	ENSP00000340797.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.072	T;T;.;T;.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	.;.;D;D;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.85	N;N;.;N;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	1.0	N;N;N;N;.;N
REVEL	Benign	0.24
Sift	Benign	0.15	T;T;T;T;.;T
Sift4G	Uncertain	0.039	D;D;D;D;.;.
Polyphen		0.036	B;B;.;B;.;.
Vest4		0.49
MutPred		0.74		Gain of glycosylation at R139 (P = 0.0406);Gain of glycosylation at R139 (P = 0.0406);.;Gain of glycosylation at R139 (P = 0.0406);.;Gain of glycosylation at R139 (P = 0.0406);
MVP		0.20
MPC		1.2
ClinPred		0.61	D
GERP RS		4.1
Varity_R		0.14
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr11-6479026;