Genetic Variant NM_001004342.5:c.748C>A (chr1-231163717-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001004342.5(TRIM67):c.748C>A(p.Leu250Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM67
NM_001004342.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.695

Publications

0 publications found

Variant links:

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]

TRIM67 links:

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ACMG classification

Classification was made for transcript

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_001004342.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM67	NM_001004342.5	MANE Select	c.748C>A	p.Leu250Met	missense	Exon 1 of 10	NP_001004342.3
TRIM67	NM_001410937.1		c.748C>A	p.Leu250Met	missense	Exon 1 of 10	NP_001397866.1	F8W8C1
TRIM67	NM_001300889.3		c.628C>A	p.Leu210Met	missense splice_region	Exon 2 of 12	NP_001287818.1	Q6ZTA4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM67	ENST00000366653.6	TSL:1 MANE Select	c.748C>A	p.Leu250Met	missense	Exon 1 of 10	ENSP00000355613.5	Q6ZTA4-3
TRIM67	ENST00000449018.7	TSL:1	c.628C>A	p.Leu210Met	missense splice_region	Exon 2 of 12	ENSP00000400163.3	Q6ZTA4-2
TRIM67	ENST00000444294.7	TSL:5	c.748C>A	p.Leu250Met	missense	Exon 1 of 10	ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1350324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665732

African (AFR)

AF:

0.00

AC:

AN:

27222

American (AMR)

AF:

0.00

AC:

AN:

30122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23788

East Asian (EAS)

AF:

0.00

AC:

AN:

29928

South Asian (SAS)

AF:

0.00

AC:

AN:

74664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1059048

Other (OTH)

AF:

0.00

AC:

AN:

55922

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

0.18

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.86

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.81

PhyloP100

0.69

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.35

MutPred

0.24

Gain of methylation at K247 (P = 0.0872)

MVP

0.76

MPC

1.5

ClinPred

0.82

GERP RS

2.4

Varity_R

0.50

gMVP

0.43

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over