Genetic Variant TRNP1:p.Gly85Ser (chr1-26994039-G-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_001013642.3(TRNP1):c.253G>A(p.Gly85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,233,926 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

TRNP1
NM_001013642.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.316

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=0.11368349).

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.253G>A	p.Gly85Ser	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.253G>A	p.Gly85Ser	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.253G>A	p.Gly85Ser	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150988

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:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1082938

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

513658

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22606

American (AMR)

AF:

0.00

AC:

AN:

8138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14080

East Asian (EAS)

AF:

0.00

AC:

AN:

26054

South Asian (SAS)

AF:

0.00

AC:

AN:

22408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2904

European-Non Finnish (NFE)

AF:

0.0000260

AC:

AN:

921984

Other (OTH)

AF:

0.00

AC:

AN:

43362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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

AF:

0.0000199

AC:

AN:

150988

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73696

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41210

American (AMR)

AF:

0.00

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5082

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

67664

Other (OTH)

AF:

0.00

AC:

AN:

2066

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

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

0.099

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.019

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.37

M_CAP

Benign

0.071

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.32

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.2

REVEL

Benign

0.083

Sift

Benign

0.21

Sift4G

Benign

0.27

Polyphen

0.90

Vest4

0.074

MutPred

0.14

Gain of glycosylation at G85 (P = 0.0056)

MVP

0.014

ClinPred

0.45

GERP RS

2.4

PromoterAI

-0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.046

gMVP

0.14

Mutation Taster

=79/21

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