Genetic Variant TRIM35:p.Ala472Thr (chr8-27287618-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_171982.5(TRIM35):c.1414G>A(p.Ala472Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,606,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TRIM35
NM_171982.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Publications

2 publications found

Variant links:

Genes affected

TRIM35 (HGNC:16285): (tripartite motif containing 35) 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. The function of this protein has not been identified. [provided by RefSeq, Jul 2008]

TRIM35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.009239346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171982.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM35	NM_171982.5	MANE Select	c.1414G>A	p.Ala472Thr	missense	Exon 6 of 6	NP_741983.2	Q9UPQ4-1
TRIM35	NM_001362813.2		c.*494G>A		3_prime_UTR	Exon 5 of 5	NP_001349742.1
TRIM35	NM_001304495.2		c.*494G>A		3_prime_UTR	Exon 4 of 4	NP_001291424.1	E5RGB3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM35	ENST00000305364.9	TSL:1 MANE Select	c.1414G>A	p.Ala472Thr	missense	Exon 6 of 6	ENSP00000301924.4	Q9UPQ4-1
TRIM35	ENST00000853030.1		c.652G>A	p.Ala218Thr	missense	Exon 2 of 2	ENSP00000523089.1
TRIM35	ENST00000521283.1	TSL:2	c.288+418G>A		intron	N/A	ENSP00000429356.1	H0YBF3

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000265

AC:

AN:

234004

AF XY:

0.000245

show subpopulations

Gnomad AFR exome

AF:

0.0000694

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000111

AC:

162

AN:

1454346

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

722766

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33404

American (AMR)

AF:

0.00128

AC:

AN:

43816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25812

East Asian (EAS)

AF:

0.00

AC:

AN:

39488

South Asian (SAS)

AF:

0.0000353

AC:

AN:

84894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000713

AC:

AN:

1108566

Other (OTH)

AF:

0.000383

AC:

AN:

60046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000335

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41592

American (AMR)

AF:

0.00176

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.72

M_CAP

Benign

0.023

MetaRNN

Benign

0.0092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.29

PhyloP100

1.3

PrimateAI

Benign

0.37

PROVEAN

Benign

0.58

REVEL

Benign

0.083

Sift

Benign

0.58

Sift4G

Benign

0.56

Polyphen

0.050

Vest4

0.072

MVP

0.49

MPC

0.44

ClinPred

0.027

GERP RS

4.0

Varity_R

0.031

gMVP

0.28

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over