Genetic Variant NM_001013642.3:c.287C>G (chr1-26994073-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001013642.3(TRNP1):c.287C>G(p.Ala96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 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. A96V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRNP1
NM_001013642.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.1546905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNP1	NM_001013642.3 link	c.287C>G	p.Ala96Gly	missense_variant	Exon 1 of 2	ENST00000522111.3	NP_001013664.2	Q6NT89A0A8E5N8C3
TRNP1	XM_005245867.4 link	c.287C>G	p.Ala96Gly	missense_variant	Exon 1 of 2		XP_005245924.1	Q6NT89

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRNP1	ENST00000522111.3 link	c.287C>G	p.Ala96Gly	missense_variant	Exon 1 of 2	1	NM_001013642.3	ENSP00000429216.2		Q6NT89
TRNP1	ENST00000531285.1 link	c.-248C>G		upstream_gene_variant		2		ENSP00000436467.2		H0YES3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149922

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1065188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

504372

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

149922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73216

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.078

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.33

M_CAP

Benign

0.037

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.095

Sift

Benign

0.092

Sift4G

Benign

0.17

Polyphen

0.92

Vest4

0.15

MutPred

0.17

Gain of relative solvent accessibility (P = 0.0166);

MVP

0.014

ClinPred

0.43

GERP RS

2.1

Varity_R

0.11

gMVP

0.21

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over