9-128822450-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004435.2(ENDOG):c.734G>T(p.Arg245Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00202 in 1,585,460 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R245C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 9 hom. )

Consequence

ENDOG
NM_004435.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.16

Variant links:

Genes affected

ENDOG (HGNC:3346): (endonuclease G) The protein encoded by this gene is a nuclear encoded endonuclease that is localized in the mitochondrion. The encoded protein is widely distributed among animals and cleaves DNA at GC tracts. This protein is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA. [provided by RefSeq, Jul 2008]

ENDOG links:

SPOUT1 (HGNC:26933): (SPOUT domain containing methyltransferase 1) Enables miRNA binding activity. Involved in maintenance of centrosome location and production of miRNAs involved in gene silencing by miRNA. Located in kinetochore; mitotic spindle; and spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2022]

SPOUT1 links:

ENSG00000286112 (HGNC:):

ENSG00000286112 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022082448).

BP6

Variant 9-128822450-G-T is Benign according to our data. Variant chr9-128822450-G-T is described in ClinVar as [Benign]. Clinvar id is 789304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENDOG	NM_004435.2 link	c.734G>T	p.Arg245Leu	missense_variant	Exon 3 of 3	ENST00000372642.5	NP_004426.2	Q14249E5KNL5
SPOUT1	NM_016390.4 link	c.*315C>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000361256.10	NP_057474.2	Q5T280

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENDOG	ENST00000372642.5 link	c.734G>T	p.Arg245Leu	missense_variant	Exon 3 of 3	1	NM_004435.2	ENSP00000361725.4	Q14249
SPOUT1	ENST00000361256 link	c.*315C>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_016390.4	ENSP00000354812.5	Q5T280
ENSG00000286112	ENST00000651925 link	c.*2485C>A		3_prime_UTR_variant	Exon 29 of 29			ENSP00000498386.1	A0A494C066
SPOUT1	ENST00000467582 link	c.*275C>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000473640.1	R4GNG4

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

223

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00227

AC:

448

AN:

197028

Hom.:

AF XY:

0.00237

AC XY:

251

AN XY:

106040

show subpopulations

Gnomad AFR exome

AF:

0.000165

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00951

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.000333

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.00270

GnomAD4 exome

AF:

0.00208

AC:

2980

AN:

1433104

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1488

AN XY:

710480

show subpopulations

Gnomad4 AFR exome

AF:

0.000366

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.00834

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00210

Gnomad4 FIN exome

AF:

0.000369

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152356

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00160

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00197

AC:

238

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

0.13

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.082

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.47

Sift

Uncertain

0.015

Sift4G

Benign

0.063

Polyphen

0.95

Vest4

0.80

MVP

0.75

MPC

1.1

ClinPred

0.033

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.38

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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