6-30154242-C-G

Variant names:

• chr6-30154242-C-G
• rs772942873
• NM_006778.4:c.1173G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006778.4(TRIM10):​c.1173G>C​(p.Lys391Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TRIM10 NM_006778.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM10	NM_006778.4	c.1173G>C	p.Lys391Asn	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.1173G>C	p.Lys391Asn	missense_variant	Exon 7 of 7	1	NM_006778.4	ENSP00000397073.2
TRIM10	ENST00000376704.3	c.1104+69G>C		intron_variant	Intron 7 of 7	1		ENSP00000365894.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245580 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133896

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460712 Hom.: 0 Cov.: 75 AF XY: 0.00000275 AC XY: 2 AN XY: 726672

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000844 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.060	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.83		Loss of ubiquitination at K391 (P = 0.013);
MVP		0.78
MPC		0.57
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.17
gMVP		0.68

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: rs772942873; hg19: chr6-30122019;