8-27287746-C-G

Variant names:

• chr8-27287746-C-G
• rs1032407682
• NM_171982.5:c.1286G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_171982.5(TRIM35):​c.1286G>C​(p.Arg429Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R429H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIM35 NM_171982.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.46
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM35	NM_171982.5	MANE Select	c.1286G>C	p.Arg429Pro	missense	Exon 6 of 6	NP_741983.2	Q9UPQ4-1
	TRIM35	NM_001362813.2		c.*366G>C		3_prime_UTR	Exon 5 of 5	NP_001349742.1
	TRIM35	NM_001304495.2		c.*366G>C		3_prime_UTR	Exon 4 of 4	NP_001291424.1	E5RGB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM35	ENST00000305364.9	TSL:1 MANE Select	c.1286G>C	p.Arg429Pro	missense	Exon 6 of 6	ENSP00000301924.4	Q9UPQ4-1
	TRIM35	ENST00000521253.1	TSL:1	c.*366G>C		3_prime_UTR	Exon 4 of 4	ENSP00000428770.1	E5RGB3
	TRIM35	ENST00000853030.1		c.524G>C	p.Arg175Pro	missense	Exon 2 of 2	ENSP00000523089.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457768 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724888

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110550

Other (OTH) AF: 0.00 AC: 0 AN: 60192

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		5.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.48	P
Vest4		0.87
MutPred		0.65		Loss of sheet (P = 0.1501)
MVP		0.82
MPC		1.5
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.92
gMVP		0.92
Mutation Taster		=42/58	disease causing

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: rs1032407682; hg19: chr8-27145263;