6-25969374-G-C

Position:

• chr6-25969374-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006355.5(TRIM38):​c.461G>C​(p.Cys154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C154F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM38 NM_006355.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0400

Genes affected

TRIM38 (HGNC:10059): (tripartite motif containing 38) This gene encodes a member of the tripartite motif (TRIM) family. The encoded protein contains a RING-type zinc finger, B box-type zinc finger and SPRY domain. The function of this protein has not been identified. A pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32880968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM38	NM_006355.5	c.461G>C	p.Cys154Ser	missense_variant	4/8	ENST00000357085.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM38	ENST00000357085.5	c.461G>C	p.Cys154Ser	missense_variant	4/8	1	NM_006355.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.461G>C (p.C154S) alteration is located in exon 4 (coding exon 2) of the TRIM38 gene. This alteration results from a G to C substitution at nucleotide position 461, causing the cysteine (C) at amino acid position 154 to be replaced by a serine (S). 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	Benign	0.32
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.7
DANN	Benign	0.36
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.10
Sift	Benign	0.18	T
Sift4G	Benign	0.52	T
Polyphen		0.60	P
Vest4		0.49
MutPred		0.44		Gain of phosphorylation at C154 (P = 0.0208);
MVP		0.63
MPC		0.78
ClinPred		0.40	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-25969602;