Variant 9-128822601-CAGTA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_004435.2(ENDOG):c.889_892del(p.Lys297GlufsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,569,174 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 18 hom. )

Consequence

ENDOG
NM_004435.2 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 357 codons.

BP6

Variant 9-128822601-CAGTA-C is Benign according to our data. Variant chr9-128822601-CAGTA-C is described in ClinVar as [Benign]. Clinvar id is 218639.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00214 (3039/1416940) while in subpopulation MID AF= 0.0233 (133/5704). AF 95% confidence interval is 0.0201. There are 18 homozygotes in gnomad4_exome. There are 1489 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ENDOG	NM_004435.2 linkuse as main transcript	c.889_892del	p.Lys297GlufsTer6	frameshift_variant	3/3	ENST00000372642.5
SPOUT1	NM_016390.4 linkuse as main transcript	c.160_163del		3_prime_UTR_variant	12/12	ENST00000361256.10
KYAT1-SPOUT1	NR_182311.1 linkuse as main transcript	n.3202_3205del		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.889_892del	p.Lys297GlufsTer6	frameshift_variant	3/3	1	NM_004435.2	P1
SPOUT1	ENST00000361256.10 linkuse as main transcript	c.160_163del		3_prime_UTR_variant	12/12	1	NM_016390.4	P1
SPOUT1	ENST00000467582.1 linkuse as main transcript	c.120_123del		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00865

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00243

AC:

436

AN:

179684

Hom.:

AF XY:

0.00228

AC XY:

218

AN XY:

95422

show subpopulations

Gnomad AFR exome

AF:

0.000546

Gnomad AMR exome

AF:

0.00677

Gnomad ASJ exome

AF:

0.00368

Gnomad EAS exome

AF:

0.00165

Gnomad SAS exome

AF:

0.000622

Gnomad FIN exome

AF:

0.0000576

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00436

GnomAD4 exome

AF:

0.00214

AC:

3039

AN:

1416940

Hom.:

AF XY:

0.00213

AC XY:

1489

AN XY:

700416

show subpopulations

Gnomad4 AFR exome

AF:

0.00100

Gnomad4 AMR exome

AF:

0.00714

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.00161

Gnomad4 SAS exome

AF:

0.000670

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00204

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152234

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000647

Hom.:

Bravo

AF:

0.00253

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jun 17, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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