6-30160434-T-A

Variant names:

• chr6-30160434-T-A
• rs774057703
• NM_006778.4:c.425A>T

Variant summary

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

The NM_006778.4(TRIM10):​c.425A>T​(p.Tyr142Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,208 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. Y142N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM10 NM_006778.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76
• 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.425A>T	p.Tyr142Phe	missense	Exon 1 of 7	NP_006769.2	Q9UDY6-1
	TRIM10	NM_052828.3		c.425A>T	p.Tyr142Phe	missense	Exon 1 of 8	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.425A>T	p.Tyr142Phe	missense	Exon 1 of 7	ENSP00000397073.2	Q9UDY6-1
	TRIM10	ENST00000376704.3	TSL:1	c.425A>T	p.Tyr142Phe	missense	Exon 1 of 8	ENSP00000365894.3	Q9UDY6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461208 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726858

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111652

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.64		Gain of disorder (P = 0.0955)
MVP		0.79
MPC		0.41
ClinPred		0.98	D
GERP RS		5.2
PromoterAI		0.018	Neutral
Varity_R		0.12
gMVP		0.14
Mutation Taster		=83/17	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: rs774057703; hg19: chr6-30128211;