Variant 1-26993916-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 14/20 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

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNP1	NM_001013642.3 linkuse as main transcript	c.130C>G	p.Pro44Ala	missense_variant	1/2	ENST00000522111.3	NP_001013664.2
TRNP1	XM_005245867.4 linkuse as main transcript	c.130C>G	p.Pro44Ala	missense_variant	1/2		XP_005245924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRNP1	ENST00000522111.3 linkuse as main transcript	c.130C>G	p.Pro44Ala	missense_variant	1/2	1	NM_001013642.3	ENSP00000429216	P1

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

GnomAD3 exomes

AF:

0.000528

AC:

AN:

13250

Hom.:

AF XY:

0.000240

AC XY:

AN XY:

8346

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 SAS exome

AF:

0.000787

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

Gnomad4 AFR exome

AF:

0.000331

Gnomad4 AMR exome

AF:

0.000183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000363

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.000960

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.000808

AC:

123

AN:

152166

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000635

Hom.:

Bravo

AF:

0.000899

ExAC

AF:

0.0000512

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

The c.130C>G (p.P44A) alteration is located in exon 1 (coding exon 1) of the TRNP1 gene. This alteration results from a C to G substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.2

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

MutationTaster

Benign

1.0

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.025

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over