7-150371485-C-T

Variant summary

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

The NM_001099695.2(REPIN1):c.415C>T(p.Arg139Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,606,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

REPIN1
NM_001099695.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

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=0.2520072).

BS2

High AC in GnomAdExome at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REPIN1	NM_001099695.2 linkuse as main transcript	c.415C>T	p.Arg139Trp	missense_variant	3/3	ENST00000489432.7
REPIN1-AS1	NR_183429.1 linkuse as main transcript	n.104-330G>A		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.415C>T	p.Arg139Trp	missense_variant	3/3	2	NM_001099695.2	P4	Q9BWE0-4
REPIN1-AS1	ENST00000488310.1 linkuse as main transcript	n.99-330G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152174

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000459

AC:

AN:

239596

Hom.:

AF XY:

0.0000684

AC XY:

AN XY:

131662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000433

AC:

AN:

1454822

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

724046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000549

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.0000579

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Nov 08, 2022

The c.415C>T (p.R139W) alteration is located in exon 3 (coding exon 2) of the REPIN1 gene. This alteration results from a C to T substitution at nucleotide position 415, causing the arginine (R) at amino acid position 139 to be replaced by a tryptophan (W). 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

0.25

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Benign

-0.23

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.53

M_CAP

Benign

0.073

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.90

MutationTaster

Benign

0.85

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

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.17

Sift4G

Pathogenic

0.0

Vest4

0.27

MVP

0.74

ClinPred

0.67

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over