rs538233068

Variant names:

• chr6-25969374-G-A
• NM_006355.5:c.461G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-25969374-G-A
• chr6-25969374-G-C
• chr6-25969374-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006355.5(TRIM38):​c.461G>A​(p.Cys154Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. C154F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM38 NM_006355.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11118072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM38	NM_006355.5	c.461G>A	p.Cys154Tyr	missense_variant	Exon 4 of 8	ENST00000357085.5	NP_006346.1
TRIM38	XM_047418080.1	c.461G>A	p.Cys154Tyr	missense_variant	Exon 4 of 9		XP_047274036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM38	ENST00000357085.5	c.461G>A	p.Cys154Tyr	missense_variant	Exon 4 of 8	1	NM_006355.5	ENSP00000349596.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460736 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726616

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.4
DANN	Benign	0.62
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.27
MutPred		0.36		Gain of phosphorylation at C154 (P = 0.031);
MVP		0.60
MPC		0.39
ClinPred		0.41	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.32

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;