Genetic Variant TRIM67:p.His98Asn (chr1-231163261-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004342.5(TRIM67):c.292C>A(p.His98Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,361,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. H98Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

TRIM67
NM_001004342.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

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:

ENSG00000295849 (HGNC:):

ENSG00000295849 links:

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ACMG classification

Classification was made for transcript

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=0.11681843).

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.292C>A	p.His98Asn	missense	Exon 1 of 10	NP_001004342.3
TRIM67	NM_001410937.1		c.292C>A	p.His98Asn	missense	Exon 1 of 10	NP_001397866.1	F8W8C1
TRIM67	NM_001300889.3		c.172C>A	p.His58Asn	missense	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.292C>A	p.His98Asn	missense	Exon 1 of 10	ENSP00000355613.5	Q6ZTA4-3
TRIM67	ENST00000449018.7	TSL:1	c.172C>A	p.His58Asn	missense	Exon 2 of 12	ENSP00000400163.3	Q6ZTA4-2
TRIM67	ENST00000444294.7	TSL:5	c.292C>A	p.His98Asn	missense	Exon 1 of 10	ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1361772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670796

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27594

American (AMR)

AF:

0.00

AC:

AN:

32026

Ashkenazi Jewish (ASJ)

AF:

0.0000425

AC:

AN:

23514

East Asian (EAS)

AF:

0.00

AC:

AN:

31618

South Asian (SAS)

AF:

0.00

AC:

AN:

75058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5390

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063020

Other (OTH)

AF:

0.00

AC:

AN:

56300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.9

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.80

REVEL

Benign

0.097

Sift

Uncertain

0.025

Sift4G

Benign

0.47

Polyphen

0.097

Vest4

0.18

MutPred

0.14

Loss of catalytic residue at H98 (P = 0.0666)

MVP

0.20

MPC

0.68

ClinPred

0.39

GERP RS

3.9

PromoterAI

0.091

Neutral

(source)

Varity_R

0.28

gMVP

0.27

Mutation Taster

=89/11

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over