6-30154330-C-G

Variant names:

• chr6-30154330-C-G
• rs142890374
• NM_006778.4:c.1085G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006778.4(TRIM10):​c.1085G>C​(p.Gly362Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: TRIM10 NM_006778.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.619

Genes affected

TRIM10 (HGNC:10072): (tripartite motif containing 10) 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. This protein localizes to cytoplasmic bodies. Studies in mice suggest that this protein plays a role in terminal differentiation of erythroid cells. Alternate splicing of this gene generates two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1601241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM10	NM_006778.4	c.1085G>C	p.Gly362Ala	missense_variant	Exon 7 of 7	ENST00000449742.7	NP_006769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM10	ENST00000449742.7	c.1085G>C	p.Gly362Ala	missense_variant	Exon 7 of 7	1	NM_006778.4	ENSP00000397073.2
TRIM10	ENST00000376704.3	c.1085G>C	p.Gly362Ala	missense_variant	Exon 7 of 8	1		ENSP00000365894.3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000446 AC: 11 AN: 246518 AF XY: 0.0000447

Gnomad AFR exome AF: 0.0000662

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000452

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000548 AC: 80 AN: 1460784 Hom.: 0 Cov.: 76 AF XY: 0.0000578 AC XY: 42 AN XY: 726704

Gnomad4 AFR exome AF: 0.0000597 AC: 2 AN: 33480

Gnomad4 AMR exome AF: 0.0000224 AC: 1 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39700

Gnomad4 SAS exome AF: 0.000151 AC: 13 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52324

Gnomad4 NFE exome AF: 0.0000531 AC: 59 AN: 1112010

Gnomad4 Remaining exome AF: 0.0000662 AC: 4 AN: 60384

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74368

Gnomad4 AFR AF: 0.0000724 AC: 0.0000723764 AN: 0.0000723764

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000206954 AN: 0.000206954

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000441 AC: 0.0000440878 AN: 0.0000440878

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000593 AC: 7

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1085G>C (p.G362A) alteration is located in exon 7 (coding exon 7) of the TRIM10 gene. This alteration results from a G to C substitution at nucleotide position 1085, causing the glycine (G) at amino acid position 362 to be replaced by an alanine (A). 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	0.091
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.46
DANN	Benign	0.54
DEOGEN2	Benign	0.0029	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.055	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.060	N;N
REVEL	Benign	0.066
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.20	B;B
Vest4		0.052
MutPred		0.66		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.60
MPC		0.12
ClinPred		0.029	T
GERP RS		-1.3
Varity_R		0.020
gMVP		0.31
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs142890374; hg19: chr6-30122107;