rs777582053

Variant names:

• chr8-27287854-C-G
• rs777582053
• NM_171982.5:c.1178G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-27287854-C-G
• chr8-27287854-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_171982.5(TRIM35):​c.1178G>C​(p.Arg393Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R393H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TRIM35 NM_171982.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM35	NM_171982.5	c.1178G>C	p.Arg393Pro	missense_variant	Exon 6 of 6	ENST00000305364.9	NP_741983.2
TRIM35	XM_047421602.1	c.728G>C	p.Arg243Pro	missense_variant	Exon 6 of 6		XP_047277558.1
TRIM35	NM_001362813.2	c.*258G>C		3_prime_UTR_variant	Exon 5 of 5		NP_001349742.1
TRIM35	NM_001304495.2	c.*258G>C		3_prime_UTR_variant	Exon 4 of 4		NP_001291424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM35	ENST00000305364.9	c.1178G>C	p.Arg393Pro	missense_variant	Exon 6 of 6	1	NM_171982.5	ENSP00000301924.4
TRIM35	ENST00000521253	c.*258G>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000428770.1
TRIM35	ENST00000521283.1	c.288+182G>C		intron_variant	Intron 4 of 4	2		ENSP00000429356.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.30
Sift	Benign	0.14	T
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.47		Gain of glycosylation at S394 (P = 0.0859);
MVP		0.69
MPC		1.5
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.46
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs777582053; hg19: chr8-27145371;