Variant X-72205359-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_017669.4(ERCC6L):c.3408C>T(p.Gly1136Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,210,259 control chromosomes in the GnomAD database, including 4 homozygotes. There are 169 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00042 ( 3 hom. 160 hem. )

Consequence

ERCC6L
NM_017669.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.68

Variant links:

Genes affected

ERCC6L (HGNC:20794): (ERCC excision repair 6 like, spindle assembly checkpoint helicase) This gene encodes a member of the SWItch/Sucrose Non-Fermentable (SWI/SNF2) family of proteins, and contains a SNF2-like ATPase domain and a PICH family domain. One distinguishing feature of this SWI/SNF protein family member is that during interphase, the protein is excluded from the nucleus, and only associates with chromatin after the nuclear envelope has broken down. This protein is a DNA translocase that is thought to bind double-stranded DNA that is exposed to stretching forces, such as those exerted by the mitotic spindle. This protein associates with ribosomal DNA and ultra-fine DNA bridges (UFBs), fine structures that connect sister chromatids during anaphase at some sites such as fragile sites, telomeres and centromeres. This gene is required for the faithful segregation of sister chromatids during mitosis, and the ATPase activity of this protein required for the resolution of UFBs before cytokinesis. [provided by RefSeq, May 2017]

ERCC6L links:

PIN4 (HGNC:8992): (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

PIN4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-72205359-G-A is Benign according to our data. Variant chrX-72205359-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660907.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.68 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC6L	NM_017669.4 link	c.3408C>T	p.Gly1136Gly	synonymous_variant	Exon 2 of 2	ENST00000334463.4	NP_060139.2	Q2NKX8
ERCC6L	NM_001009954.3 link	c.3039C>T	p.Gly1013Gly	synonymous_variant	Exon 3 of 3		NP_001009954.1
PIN4	NM_001170747.1 link	c.312+8455G>A		intron_variant	Intron 3 of 3		NP_001164218.1	Q9Y237-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6L	ENST00000334463.4 link	c.3408C>T	p.Gly1136Gly	synonymous_variant	Exon 2 of 2	1	NM_017669.4	ENSP00000334675.3		Q2NKX8

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

112240

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

AN XY:

34402

show subpopulations

Gnomad AFR

AF:

0.000129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

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:

0.000563

Gnomad OTH

AF:

0.00398

GnomAD3 exomes

AF:

0.000426

AC:

AN:

183137

Hom.:

AF XY:

0.000473

AC XY:

AN XY:

67679

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000474

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000315

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.000600

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.000415

AC:

456

AN:

1097965

Hom.:

Cov.:

AF XY:

0.000440

AC XY:

160

AN XY:

363325

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.000846

GnomAD4 genome

AF:

0.000374

AC:

AN:

112294

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

34466

show subpopulations

Gnomad4 AFR

AF:

0.000129

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000563

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000589

EpiCase

AF:

0.00109

EpiControl

AF:

0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ERCC6L: BP4, BP7, BS2; PIN4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.041

DANN

Benign

0.85

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