dbSNP rs148656966: ERCC6L:p.Gly1136Gly (chrX-72205359-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017669.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERCC6L	NM_017669.4	MANE Select	c.3408C>T	p.Gly1136Gly	synonymous	Exon 2 of 2	NP_060139.2
ERCC6L	NM_001009954.3		c.3039C>T	p.Gly1013Gly	synonymous	Exon 3 of 3	NP_001009954.1	B5MDQ0
PIN4	NM_001170747.1		c.312+8455G>A		intron	N/A	NP_001164218.1	Q9Y237-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERCC6L	ENST00000334463.4	TSL:1 MANE Select	c.3408C>T	p.Gly1136Gly	synonymous	Exon 2 of 2	ENSP00000334675.3	Q2NKX8
ERCC6L	ENST00000373657.2	TSL:2	c.3039C>T	p.Gly1013Gly	synonymous	Exon 3 of 3	ENSP00000362761.1	B5MDQ0
PIN4	ENST00000423432.6	TSL:2	c.312+8455G>A		intron	N/A	ENSP00000409154.2	Q9Y237-3

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

112240

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000426

AC:

AN:

183137

AF XY:

0.000473

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 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

African (AFR)

AF:

0.000152

AC:

AN:

26399

American (AMR)

AF:

0.000483

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19377

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.000406

AC:

AN:

54135

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00822

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.000403

AC:

339

AN:

841905

Other (OTH)

AF:

0.000846

AC:

AN:

46089

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000374

AC:

AN:

112294

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

34466

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

30962

American (AMR)

AF:

0.000189

AC:

AN:

10583

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3568

South Asian (SAS)

AF:

0.00

AC:

AN:

2692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000563

AC:

AN:

53252

Other (OTH)

AF:

0.00393

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000589

EpiCase

AF:

0.00109

EpiControl

AF:

0.00148

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.041

(source)

DANN

Benign

0.85

PhyloP100

-4.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over