rs1175565710

Variant names:

• chr1-231163244-C-G
• rs1175565710
• NM_001004342.5:c.275C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-231163244-C-G
• chr1-231163244-C-T

Variant summary

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

The NM_001004342.5(TRIM67):​c.275C>G​(p.Ala92Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000443 in 1,353,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. A92T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: TRIM67 NM_001004342.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121679336).

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.275C>G	p.Ala92Gly	missense	Exon 1 of 10	NP_001004342.3
	TRIM67	NM_001410937.1		c.275C>G	p.Ala92Gly	missense	Exon 1 of 10	NP_001397866.1	F8W8C1
	TRIM67	NM_001300889.3		c.155C>G	p.Ala52Gly	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.275C>G	p.Ala92Gly	missense	Exon 1 of 10	ENSP00000355613.5	Q6ZTA4-3
	TRIM67	ENST00000449018.7	TSL:1	c.155C>G	p.Ala52Gly	missense	Exon 2 of 12	ENSP00000400163.3	Q6ZTA4-2
	TRIM67	ENST00000444294.7	TSL:5	c.275C>G	p.Ala92Gly	missense	Exon 1 of 10	ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000443 AC: 6 AN: 1353410 Hom.: 0 Cov.: 31 AF XY: 0.00000300 AC XY: 2 AN XY: 666208

African (AFR) AF: 0.00 AC: 0 AN: 27350

American (AMR) AF: 0.00 AC: 0 AN: 30980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23004

East Asian (EAS) AF: 0.00 AC: 0 AN: 31200

South Asian (SAS) AF: 0.00 AC: 0 AN: 73724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5198

European-Non Finnish (NFE) AF: 0.00000566 AC: 6 AN: 1059242

Other (OTH) AF: 0.00 AC: 0 AN: 55986

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.020
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.092
Sift	Benign	0.52	T
Sift4G	Benign	0.43	T
Polyphen		0.45	B
Vest4		0.18
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.25
MPC		0.58
ClinPred		0.15	T
GERP RS		2.8
PromoterAI		0.11	Neutral
Varity_R		0.13
gMVP		0.29
Mutation Taster		=94/6	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: rs1175565710; hg19: chr1-231298990;