Variant chr7-150371543-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001099695.2(REPIN1):c.473C>G(p.Ala158Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 1,452,718 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: not found (cov: 34)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

REPIN1
NM_001099695.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.286

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22194251).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REPIN1	NM_001099695.2 linkuse as main transcript	c.473C>G	p.Ala158Gly	missense_variant	3/3	ENST00000489432.7
REPIN1-AS1	NR_183429.1 linkuse as main transcript	n.104-388G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REPIN1	ENST00000489432.7 linkuse as main transcript	c.473C>G	p.Ala158Gly	missense_variant	3/3	2	NM_001099695.2	P4	Q9BWE0-4
REPIN1-AS1	ENST00000488310.1 linkuse as main transcript	n.99-388G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000895

AC:

AN:

1452718

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

722996

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:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 12, 2021

The c.473C>G (p.A158G) alteration is located in exon 3 (coding exon 2) of the REPIN1 gene. This alteration results from a C to G substitution at nucleotide position 473, causing the alanine (A) at amino acid position 158 to be replaced by a glycine (G). 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

0.20

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

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

Eigen

Benign

0.17

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.71

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

M_CAP

Benign

0.023

MetaRNN

Benign

0.22

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

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.5

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

MutationTaster

Benign

1.0

D;D;D;N;N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

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

REVEL

Benign

0.077

Sift

Uncertain

0.021

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

Sift4G

Uncertain

0.056

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

Polyphen

1.0

.;D;D;.;.;.;D

Vest4

0.31, 0.32, 0.40, 0.31

MutPred

0.27

Loss of stability (P = 0.0815);Loss of stability (P = 0.0815);Loss of stability (P = 0.0815);.;.;.;Loss of stability (P = 0.0815);

MVP

0.47

MPC

1.7

ClinPred

0.55

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over