chr1-231163396-C-T

Variant names:

• chr1-231163396-C-T
• rs753735570
• NM_001004342.5:c.427C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004342.5(TRIM67):​c.427C>T​(p.Arg143Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,535,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: TRIM67 NM_001004342.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.346
• Publications: 1 publications found

Genes affected

TRIM67 (HGNC:31859): (tripartite motif containing 67) Predicted to enable zinc ion binding activity. Predicted to be involved in regulation of protein localization. Predicted to act upstream of or within negative regulation of Ras protein signal transduction; positive regulation of neuron projection development; and positive regulation of ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000295849 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27613223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004342.5. 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
	TRIM67	NM_001004342.5	MANE Select	c.427C>T	p.Arg143Trp	missense	Exon 1 of 10	NP_001004342.3
	TRIM67	NM_001410937.1		c.427C>T	p.Arg143Trp	missense	Exon 1 of 10	NP_001397866.1	F8W8C1
	TRIM67	NM_001300889.3		c.307C>T	p.Arg103Trp	missense	Exon 2 of 12	NP_001287818.1	Q6ZTA4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM67	ENST00000366653.6	TSL:1 MANE Select	c.427C>T	p.Arg143Trp	missense	Exon 1 of 10	ENSP00000355613.5	Q6ZTA4-3
	TRIM67	ENST00000449018.7	TSL:1	c.307C>T	p.Arg103Trp	missense	Exon 2 of 12	ENSP00000400163.3	Q6ZTA4-2
	TRIM67	ENST00000444294.7	TSL:5	c.427C>T	p.Arg143Trp	missense	Exon 1 of 10	ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 4 AN: 125968 AF XY: 0.0000289

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000431

Gnomad ASJ exome AF: 0.000131

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000218

Gnomad OTH exome AF: 0.000264

GnomAD4 exome AF: 0.0000166 AC: 23 AN: 1383698 Hom.: 0 Cov.: 31 AF XY: 0.0000147 AC XY: 10 AN XY: 682572

African (AFR) AF: 0.00 AC: 0 AN: 29540

American (AMR) AF: 0.0000573 AC: 2 AN: 34920

Ashkenazi Jewish (ASJ) AF: 0.000445 AC: 11 AN: 24726

East Asian (EAS) AF: 0.00 AC: 0 AN: 34472

South Asian (SAS) AF: 0.00 AC: 0 AN: 77712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5352

European-Non Finnish (NFE) AF: 0.00000744 AC: 8 AN: 1075226

Other (OTH) AF: 0.0000347 AC: 2 AN: 57578

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000479 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000544 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.35
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.29
Sift	Uncertain	0.022	D
Sift4G	Benign	0.078	T
Polyphen		0.97	D
Vest4		0.29
MutPred		0.35		Loss of methylation at R143 (P = 0.0095)
MVP		0.70
MPC		0.82
ClinPred		0.20	T
GERP RS		4.3
PromoterAI		0.0022	Neutral
Varity_R		0.15
gMVP		0.57
Mutation Taster		=95/5	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: rs753735570; hg19: chr1-231299142;