chr1-228401056-C-T

Variant names:

• chr1-228401056-C-T
• rs558730848
• NM_145214.3:c.643G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145214.3(TRIM11):​c.643G>A​(p.Ala215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: TRIM11 NM_145214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.17
• Publications: 3 publications found

Genes affected

TRIM11 (HGNC:16281): (tripartite motif containing 11) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. 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 the nucleus and the cytoplasm. Its function has not been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029768616).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145214.3. 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
	TRIM11	NM_145214.3	MANE Select	c.643G>A	p.Ala215Thr	missense	Exon 3 of 6	NP_660215.1	Q96F44-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM11	ENST00000284551.11	TSL:1 MANE Select	c.643G>A	p.Ala215Thr	missense	Exon 3 of 6	ENSP00000284551.6	Q96F44-1
	TRIM11	ENST00000493030.6	TSL:1	c.268G>A	p.Ala90Thr	missense	Exon 2 of 5	ENSP00000473360.1	R4GMV1
	TRIM11	ENST00000946665.1		c.643G>A	p.Ala215Thr	missense	Exon 3 of 6	ENSP00000616724.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000451 AC: 11 AN: 243968 AF XY: 0.0000376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000920

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460150 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726410

African (AFR) AF: 0.0000299 AC: 1 AN: 33450

American (AMR) AF: 0.000247 AC: 11 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111548

Other (OTH) AF: 0.000149 AC: 9 AN: 60338

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74496

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.00124 AC: 19 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.000253

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.2
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.010
Sift	Benign	0.39	T
Sift4G	Benign	0.58	T
Polyphen		0.067	B
Vest4		0.18
MutPred		0.36		Gain of phosphorylation at A215 (P = 0.0441)
MVP		0.043
MPC		0.38
ClinPred		0.026	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.053
gMVP		0.39
Mutation Taster		=100/0	polymorphism

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: rs558730848; hg19: chr1-228588757; COSMIC: COSV52859707; COSMIC: COSV52859707;