Variant 7-150371512-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099695.2(REPIN1):c.442G>A(p.Gly148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,606,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

REPIN1
NM_001099695.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

REPIN1 (HGNC:17922): (replication initiator 1) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of glucose import and regulation of fatty acid transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

REPIN1 links:

REPIN1-AS1 (HGNC:41201): (REPIN1 antisense RNA 1)

REPIN1-AS1 links:

ZNF775 (HGNC:28501): (zinc finger protein 775) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF775 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24775061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REPIN1	NM_001099695.2 linkuse as main transcript	c.442G>A	p.Gly148Ser	missense_variant	3/3	ENST00000489432.7	NP_001093165.1
REPIN1-AS1	NR_183429.1 linkuse as main transcript	n.104-357C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REPIN1	ENST00000489432.7 linkuse as main transcript	c.442G>A	p.Gly148Ser	missense_variant	3/3	2	NM_001099695.2	ENSP00000417291	P4	Q9BWE0-4
REPIN1-AS1	ENST00000488310.1 linkuse as main transcript	n.99-357C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

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:

6.88e-7

AC:

AN:

1454264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723824

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Apr 29, 2024

The c.442G>A (p.G148S) alteration is located in exon 3 (coding exon 2) of the REPIN1 gene. This alteration results from a G to A substitution at nucleotide position 442, causing the glycine (G) at amino acid position 148 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T;T;.;T;T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.78

T;.;T;T;T;T;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.25

T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.5

.;L;L;.;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.3

D;D;D;D;D;D;D

REVEL

Benign

0.044

Sift

Uncertain

0.012

D;D;D;D;D;D;D

Sift4G

Benign

0.097

T;D;D;D;D;D;D

Polyphen

0.86

.;P;P;.;.;.;P

Vest4

0.14, 0.13, 0.16, 0.14

MutPred

0.47

Gain of glycosylation at P88 (P = 0.0909);Gain of glycosylation at P88 (P = 0.0909);Gain of glycosylation at P88 (P = 0.0909);.;.;.;Gain of glycosylation at P88 (P = 0.0909);

MVP

0.62

MPC

0.89

ClinPred

0.72

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.096

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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