Genetic Variant TRNP1:p.Leu70Arg (chr1-26993995-T-G) – 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_001013642.3(TRNP1):c.209T>G(p.Leu70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,296,374 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. 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. L70P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

TRNP1
NM_001013642.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0720

Publications

0 publications found

Variant links:

Genes affected

TRNP1 (HGNC:34348): (TMF1 regulated nuclear protein 1) Predicted to enable DNA binding activity. Predicted to be involved in several processes, including cerebellar cortex morphogenesis; neural precursor cell proliferation; and regulation of cell population proliferation. Predicted to be active in nucleus. Predicted to colocalize with euchromatin. [provided by Alliance of Genome Resources, Apr 2022]

TRNP1 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=0.22375995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013642.3. 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
	TRNP1	NM_001013642.3	MANE Select	c.209T>G	p.Leu70Arg	missense	Exon 1 of 2	NP_001013664.2	Q6NT89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNP1	ENST00000522111.3	TSL:1 MANE Select	c.209T>G	p.Leu70Arg	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.209T>G	p.Leu70Arg	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.73e-7

AC:

AN:

1144954

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

551966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23340

American (AMR)

AF:

0.00

AC:

AN:

9300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15786

East Asian (EAS)

AF:

0.00

AC:

AN:

26998

South Asian (SAS)

AF:

0.00

AC:

AN:

38426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3324

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

956624

Other (OTH)

AF:

0.00

AC:

AN:

46066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151420

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73956

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41250

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5054

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67830

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.041

Eigen

Benign

0.11

Eigen_PC

Benign

0.035

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

0.072

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Benign

0.065

Polyphen

0.99

Vest4

0.38

MutPred

0.28

Gain of MoRF binding (P = 0.0206)

MVP

0.35

ClinPred

0.68

GERP RS

1.4

PromoterAI

0.083

Neutral

(source)

Varity_R

0.54

gMVP

0.34

Mutation Taster

=91/9

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

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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