Variant 9-128822370-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004435.2(ENDOG):c.654C>T(p.Ile218=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,613,898 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 125 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 124 hom. )

Consequence

ENDOG
NM_004435.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.12

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:

KYAT1-SPOUT1 (HGNC:):

KYAT1-SPOUT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-128822370-C-T is Benign according to our data. Variant chr9-128822370-C-T is described in ClinVar as [Benign]. Clinvar id is 774205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ENDOG	NM_004435.2 linkuse as main transcript	c.654C>T	p.Ile218=	synonymous_variant	3/3	ENST00000372642.5
SPOUT1	NM_016390.4 linkuse as main transcript	c.*395G>A		3_prime_UTR_variant	12/12	ENST00000361256.10
KYAT1-SPOUT1	NR_182311.1 linkuse as main transcript	n.3437G>A		non_coding_transcript_exon_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ENDOG	ENST00000372642.5 linkuse as main transcript	c.654C>T	p.Ile218=	synonymous_variant	3/3	1	NM_004435.2	P1
SPOUT1	ENST00000361256.10 linkuse as main transcript	c.*395G>A		3_prime_UTR_variant	12/12	1	NM_016390.4	P1
SPOUT1	ENST00000467582.1 linkuse as main transcript	c.*355G>A		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3378

AN:

152194

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0767

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00930

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00605

AC:

1499

AN:

247948

Hom.:

AF XY:

0.00441

AC XY:

593

AN XY:

134458

show subpopulations

Gnomad AFR exome

AF:

0.0778

Gnomad AMR exome

AF:

0.00487

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000307

Gnomad OTH exome

AF:

0.00312

GnomAD4 exome

AF:

0.00240

AC:

3510

AN:

1461586

Hom.:

124

Cov.:

AF XY:

0.00208

AC XY:

1514

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0817

Gnomad4 AMR exome

AF:

0.00532

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00508

GnomAD4 genome

AF:

0.0223

AC:

3390

AN:

152312

Hom.:

125

Cov.:

AF XY:

0.0213

AC XY:

1589

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0768

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.9

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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