Genetic Variant TRNP1:p.Pro44Ala (chr1-26993916-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013642.3(TRNP1):c.130C>G(p.Pro44Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,369,736 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

TRNP1
NM_001013642.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.512

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048143268).

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.130C>G	p.Pro44Ala	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.130C>G	p.Pro44Ala	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.130C>G	p.Pro44Ala	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes

AF:

0.000809

AC:

123

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000528

AC:

AN:

13250

AF XY:

0.000240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000685

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000595

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00158

AC:

1918

AN:

1217570

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

912

AN XY:

593586

show subpopulations

African (AFR)

AF:

0.000331

AC:

AN:

24160

American (AMR)

AF:

0.000183

AC:

AN:

10938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17882

East Asian (EAS)

AF:

0.0000363

AC:

AN:

27514

South Asian (SAS)

AF:

0.000626

AC:

AN:

52692

European-Finnish (FIN)

AF:

0.000960

AC:

AN:

29174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4176

European-Non Finnish (NFE)

AF:

0.00178

AC:

1780

AN:

1001068

Other (OTH)

AF:

0.00132

AC:

AN:

49966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

118

235

353

470

588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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

AF:

0.000808

AC:

123

AN:

152166

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41560

American (AMR)

AF:

0.000327

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00134

AC:

AN:

67950

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000635

Hom.:

Bravo

AF:

0.000899

ExAC

AF:

0.0000512

AC:

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

Benign

0.054

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.2

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.031

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.33

M_CAP

Benign

0.0010

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.51

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.74

REVEL

Benign

0.011

Sift

Benign

1.0

Sift4G

Benign

0.20

Polyphen

0.0070

Vest4

0.091

MVP

0.014

ClinPred

0.034

GERP RS

-1.7

PromoterAI

-0.092

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.025

gMVP

0.31

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over