11-6456225-C-T

Variant names:

• chr11-6456225-C-T
• rs13343175
• NM_033278.4:c.1430-50G>A

Variant summary

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

The NM_033278.4(TRIM3):​c.1430-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,606,772 control chromosomes in the GnomAD database, including 32,618 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 0.22 (3961 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28657 hom.)
• Consequence: TRIM3 NM_033278.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

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.1430-50G>A		intron	N/A	NP_150594.2
	TRIM3	NM_001248006.2		c.1430-50G>A		intron	N/A	NP_001234935.1	O75382-1
	TRIM3	NM_006458.4		c.1430-50G>A		intron	N/A	NP_006449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	ENST00000345851.8	TSL:1 MANE Select	c.1430-50G>A		intron	N/A	ENSP00000340797.3	O75382-1
	TRIM3	ENST00000527237.1	TSL:1	n.316-50G>A		intron	N/A
	TRIM3	ENST00000359518.7	TSL:5	c.1430-50G>A		intron	N/A	ENSP00000352508.3	O75382-1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32868 AN: 151966 Hom.: 3954 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.183 AC: 45413 AN: 248654 AF XY: 0.186

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.0151

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.193 AC: 281001 AN: 1454688 Hom.: 28657 Cov.: 33 AF XY: 0.195 AC XY: 140909 AN XY: 722494

African (AFR) AF: 0.314 AC: 10486 AN: 33394

American (AMR) AF: 0.145 AC: 6464 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 5986 AN: 25850

East Asian (EAS) AF: 0.0231 AC: 912 AN: 39558

South Asian (SAS) AF: 0.238 AC: 20359 AN: 85704

European-Finnish (FIN) AF: 0.135 AC: 7172 AN: 53150

Middle Eastern (MID) AF: 0.215 AC: 1237 AN: 5748

European-Non Finnish (NFE) AF: 0.195 AC: 216274 AN: 1106746

Other (OTH) AF: 0.202 AC: 12111 AN: 60084

GnomAD4 genome AF: 0.216 AC: 32902 AN: 152084 Hom.: 3961 Cov.: 32 AF XY: 0.211 AC XY: 15703 AN XY: 74384

African (AFR) AF: 0.313 AC: 12999 AN: 41474

American (AMR) AF: 0.178 AC: 2719 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3464

East Asian (EAS) AF: 0.0159 AC: 82 AN: 5170

South Asian (SAS) AF: 0.227 AC: 1091 AN: 4814

European-Finnish (FIN) AF: 0.122 AC: 1290 AN: 10598

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13264 AN: 67956

Other (OTH) AF: 0.209 AC: 441 AN: 2114

Alfa AF: 0.203 Hom.: 3703

Bravo AF: 0.223

Asia WGS AF: 0.124 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs13343175; hg19: chr11-6477455;