X-72205274-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017669.4(ERCC6L):c.3493C>T(p.Pro1165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,210,310 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 3 hem. )

Consequence

ERCC6L
NM_017669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.164

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044492513).

BS2

High Hemizygotes in GnomAd4 at 4 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.3493C>T	p.Pro1165Ser	missense	Exon 2 of 2	NP_060139.2
ERCC6L	NM_001009954.3		c.3124C>T	p.Pro1042Ser	missense	Exon 3 of 3	NP_001009954.1	B5MDQ0
PIN4	NM_001170747.1		c.312+8370G>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.3493C>T	p.Pro1165Ser	missense	Exon 2 of 2	ENSP00000334675.3	Q2NKX8
ERCC6L	ENST00000373657.2	TSL:2	c.3124C>T	p.Pro1042Ser	missense	Exon 3 of 3	ENSP00000362761.1	B5MDQ0
PIN4	ENST00000423432.6	TSL:2	c.312+8370G>A		intron	N/A	ENSP00000409154.2	Q9Y237-3

Frequencies

GnomAD3 genomes

AF:

0.0000981

AC:

AN:

112108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000665

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

182988

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.00000455

AC:

AN:

1098202

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363566

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26402

American (AMR)

AF:

0.0000852

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54139

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842105

Other (OTH)

AF:

0.00

AC:

AN:

46093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000981

AC:

AN:

112108

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34276

show subpopulations

African (AFR)

AF:

0.000130

AC:

AN:

30874

American (AMR)

AF:

0.000665

AC:

AN:

10529

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3564

South Asian (SAS)

AF:

0.00

AC:

AN:

2665

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6139

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53258

Other (OTH)

AF:

0.00

AC:

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.000200

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.34

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0091

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.2

PhyloP100

0.16

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.69

REVEL

Benign

0.16

Sift

Benign

0.45

Sift4G

Benign

0.72

Polyphen

0.0010

Vest4

0.020

MVP

0.32

MPC

0.52

ClinPred

0.0033

GERP RS

0.68

Varity_R

0.029

gMVP

0.080

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