8-27287744-C-A

Variant names:

• chr8-27287744-C-A
• rs199652032
• NM_171982.5:c.1288G>T

Variant summary

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

The NM_171982.5(TRIM35):​c.1288G>T​(p.Val430Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000453 in 1,610,172 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: TRIM35 NM_171982.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.29
• Publications: 3 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 0 ACMG points.

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.1288G>T	p.Val430Leu	missense	Exon 6 of 6	NP_741983.2	Q9UPQ4-1
	TRIM35	NM_001362813.2		c.*368G>T		3_prime_UTR	Exon 5 of 5	NP_001349742.1
	TRIM35	NM_001304495.2		c.*368G>T		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.1288G>T	p.Val430Leu	missense	Exon 6 of 6	ENSP00000301924.4	Q9UPQ4-1
	TRIM35	ENST00000521253.1	TSL:1	c.*368G>T		3_prime_UTR	Exon 4 of 4	ENSP00000428770.1	E5RGB3
	TRIM35	ENST00000853030.1		c.526G>T	p.Val176Leu	missense	Exon 2 of 2	ENSP00000523089.1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000238 AC: 57 AN: 239624 AF XY: 0.000208

Gnomad AFR exome AF: 0.000131

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000477 AC: 696 AN: 1457936 Hom.: 0 Cov.: 31 AF XY: 0.000425 AC XY: 308 AN XY: 724960

African (AFR) AF: 0.0000897 AC: 3 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25924

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.00 AC: 0 AN: 85424

European-Finnish (FIN) AF: 0.0000378 AC: 2 AN: 52934

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

European-Non Finnish (NFE) AF: 0.000610 AC: 678 AN: 1110602

Other (OTH) AF: 0.000216 AC: 13 AN: 60216

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74380

African (AFR) AF: 0.0000723 AC: 3 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000433 Hom.: 0

Bravo AF: 0.000227

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000247 AC: 30

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.015	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.61
Sift	Benign	0.041	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.69	P
Vest4		0.56
MutPred		0.68		Gain of disorder (P = 0.1344)
MVP		0.81
MPC		0.90
ClinPred		0.49	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.47
Mutation Taster		=85/15	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: rs199652032; hg19: chr8-27145261; COSMIC: COSV59522341;