NM_006778.4:c.1418G>T

Variant names:

• chr6-30153997-C-A
• rs1772262264
• NM_006778.4:c.1418G>T

Variant summary

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

The NM_006778.4(TRIM10):​c.1418G>T​(p.Arg473Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R473Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIM10 NM_006778.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 0 publications found

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006778.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM10	NM_006778.4	MANE Select	c.1418G>T	p.Arg473Leu	missense	Exon 7 of 7	NP_006769.2	Q9UDY6-1
	TRIM10	NM_052828.3		c.1105-226G>T		intron	N/A	NP_439893.2	Q9UDY6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM10	ENST00000449742.7	TSL:1 MANE Select	c.1418G>T	p.Arg473Leu	missense	Exon 7 of 7	ENSP00000397073.2	Q9UDY6-1
	TRIM10	ENST00000376704.3	TSL:1	c.1105-226G>T		intron	N/A	ENSP00000365894.3	Q9UDY6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452920 Hom.: 0 Cov.: 74 AF XY: 0.00000139 AC XY: 1 AN XY: 721018

African (AFR) AF: 0.00 AC: 0 AN: 33316

American (AMR) AF: 0.00 AC: 0 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105738

Other (OTH) AF: 0.00 AC: 0 AN: 59932

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0074	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.88
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.29
Sift	Benign	0.12	T
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.59		Loss of solvent accessibility (P = 0.001)
MVP		0.67
MPC		0.58
ClinPred		0.86	D
GERP RS		6.0
Varity_R		0.25
gMVP		0.46
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs1772262264; hg19: chr6-30121774;