9-128822370-C-T

Variant names:

• chr9-128822370-C-T
• rs55985529
• NM_004435.2:c.654C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004435.2(ENDOG):​c.654C>T​(p.Ile218Ile) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12

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]

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]

ENSG00000286112 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ENDOG	NM_004435.2	c.654C>T	p.Ile218Ile	synonymous_variant	Exon 3 of 3	ENST00000372642.5	NP_004426.2
SPOUT1	NM_016390.4	c.*395G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000361256.10	NP_057474.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENDOG	ENST00000372642.5	c.654C>T	p.Ile218Ile	synonymous_variant	Exon 3 of 3	1	NM_004435.2	ENSP00000361725.4
SPOUT1	ENST00000361256	c.*395G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_016390.4	ENSP00000354812.5
ENSG00000286112	ENST00000651925	c.*2565G>A		3_prime_UTR_variant	Exon 29 of 29			ENSP00000498386.1
SPOUT1	ENST00000467582	c.*355G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000473640.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3378 AN: 152194 Hom.: 123 Cov.: 33

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

GnomAD2 exomes AF: 0.00605 AC: 1499 AN: 247948 AF XY: 0.00441

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 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.: 31 AF XY: 0.00208 AC XY: 1514 AN XY: 727080

Gnomad4 AFR exome AF: 0.0817 AC: 2735 AN: 33476

Gnomad4 AMR exome AF: 0.00532 AC: 238 AN: 44698

Gnomad4 ASJ exome AF: 0.00134 AC: 35 AN: 26130

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39698

Gnomad4 SAS exome AF: 0.000383 AC: 33 AN: 86200

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53270

Gnomad4 NFE exome AF: 0.000119 AC: 132 AN: 1111956

Gnomad4 Remaining exome AF: 0.00508 AC: 307 AN: 60390

GnomAD4 genome AF: 0.0223 AC: 3390 AN: 152312 Hom.: 125 Cov.: 33 AF XY: 0.0213 AC XY: 1589 AN XY: 74476

Gnomad4 AFR AF: 0.0768 AC: 0.0768157 AN: 0.0768157

Gnomad4 AMR AF: 0.00928 AC: 0.00928469 AN: 0.00928469

Gnomad4 ASJ AF: 0.00115 AC: 0.00115274 AN: 0.00115274

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000414 AC: 0.00041425 AN: 0.00041425

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000162 AC: 0.000161674 AN: 0.000161674

Gnomad4 OTH AF: 0.0166 AC: 0.0165563 AN: 0.0165563

Alfa AF: 0.0120 Hom.: 42

Bravo AF: 0.0255

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 27, 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
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
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55985529; hg19: chr9-131584649;