chr11-6457154-C-T

Variant names:

• chr11-6457154-C-T
• rs11605141
• NM_033278.4:c.697-125G>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.697-125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,511,962 control chromosomes in the GnomAD database, including 30,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (3578 hom., cov: 33)
  • Exomes 𝑓: 0.19 (26447 hom.)
• Consequence: TRIM3 NM_033278.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 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.697-125G>A		intron	N/A	NP_150594.2
	TRIM3	NM_001248006.2		c.697-125G>A		intron	N/A	NP_001234935.1	O75382-1
	TRIM3	NM_006458.4		c.697-125G>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.697-125G>A		intron	N/A	ENSP00000340797.3	O75382-1
	TRIM3	ENST00000359518.7	TSL:5	c.697-125G>A		intron	N/A	ENSP00000352508.3	O75382-1
	TRIM3	ENST00000525074.5	TSL:2	c.697-125G>A		intron	N/A	ENSP00000433102.1	O75382-1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31580 AN: 152002 Hom.: 3575 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.192 AC: 261093 AN: 1359842 Hom.: 26447 Cov.: 26 AF XY: 0.194 AC XY: 129876 AN XY: 669710

African (AFR) AF: 0.282 AC: 8915 AN: 31574

American (AMR) AF: 0.142 AC: 5736 AN: 40478

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 4975 AN: 21906

East Asian (EAS) AF: 0.0232 AC: 903 AN: 38950

South Asian (SAS) AF: 0.236 AC: 17663 AN: 74878

European-Finnish (FIN) AF: 0.136 AC: 5075 AN: 37416

Middle Eastern (MID) AF: 0.218 AC: 1056 AN: 4834

European-Non Finnish (NFE) AF: 0.195 AC: 205505 AN: 1053122

Other (OTH) AF: 0.199 AC: 11265 AN: 56684

GnomAD4 genome AF: 0.208 AC: 31598 AN: 152120 Hom.: 3578 Cov.: 33 AF XY: 0.203 AC XY: 15087 AN XY: 74382

African (AFR) AF: 0.283 AC: 11737 AN: 41446

American (AMR) AF: 0.174 AC: 2664 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 845 AN: 3472

East Asian (EAS) AF: 0.0160 AC: 83 AN: 5190

South Asian (SAS) AF: 0.227 AC: 1097 AN: 4824

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10594

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

European-Non Finnish (NFE) AF: 0.195 AC: 13281 AN: 67982

Other (OTH) AF: 0.204 AC: 431 AN: 2114

Alfa AF: 0.207 Hom.: 448

Bravo AF: 0.213

Asia WGS AF: 0.121 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.61
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11605141; hg19: chr11-6478384;