8-27287861-C-A

Variant names:

• chr8-27287861-C-A
• NM_171982.5:c.1171G>T

Variant summary

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

The NM_171982.5(TRIM35):​c.1171G>T​(p.Asp391Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM35 NM_171982.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

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.1171G>T	p.Asp391Tyr	missense_variant	Exon 6 of 6	ENST00000305364.9	NP_741983.2
TRIM35	XM_047421602.1	c.721G>T	p.Asp241Tyr	missense_variant	Exon 6 of 6		XP_047277558.1
TRIM35	NM_001362813.2	c.*251G>T		3_prime_UTR_variant	Exon 5 of 5		NP_001349742.1
TRIM35	NM_001304495.2	c.*251G>T		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.1171G>T	p.Asp391Tyr	missense_variant	Exon 6 of 6	1	NM_171982.5	ENSP00000301924.4
TRIM35	ENST00000521253	c.*251G>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000428770.1
TRIM35	ENST00000521283.1	c.288+175G>T		intron_variant	Intron 4 of 4	2		ENSP00000429356.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1171G>T (p.D391Y) alteration is located in exon 6 (coding exon 6) of the TRIM35 gene. This alteration results from a G to T substitution at nucleotide position 1171, causing the aspartic acid (D) at amino acid position 391 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.90	P
Vest4		0.60
MutPred		0.56		Loss of disorder (P = 0.0466);
MVP		0.78
MPC		1.4
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.29
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-27145378;