rs2042817718

Variant names:

• chrX-72206081-A-C
• rs2042817718
• NM_017669.4:c.2686T>G

Your query was ambiguous. Multiple possible variants found:

• chrX-72206081-A-C
• chrX-72206081-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017669.4(ERCC6L):​c.2686T>G​(p.Trp896Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,066 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: ERCC6L NM_017669.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.229
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09578234).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L	NM_017669.4	MANE Select	c.2686T>G	p.Trp896Gly	missense	Exon 2 of 2	NP_060139.2
	ERCC6L	NM_001009954.3		c.2317T>G	p.Trp773Gly	missense	Exon 3 of 3	NP_001009954.1	B5MDQ0
	PIN4	NM_001170747.1		c.312+9177A>C		intron	N/A	NP_001164218.1	Q9Y237-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L	ENST00000334463.4	TSL:1 MANE Select	c.2686T>G	p.Trp896Gly	missense	Exon 2 of 2	ENSP00000334675.3	Q2NKX8
	ERCC6L	ENST00000373657.2	TSL:2	c.2317T>G	p.Trp773Gly	missense	Exon 3 of 3	ENSP00000362761.1	B5MDQ0
	PIN4	ENST00000423432.6	TSL:2	c.312+9177A>C		intron	N/A	ENSP00000409154.2	Q9Y237-3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097066 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362476

African (AFR) AF: 0.000114 AC: 3 AN: 26385

American (AMR) AF: 0.00 AC: 0 AN: 35125

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19359

East Asian (EAS) AF: 0.00 AC: 0 AN: 30190

South Asian (SAS) AF: 0.00 AC: 0 AN: 53915

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841404

Other (OTH) AF: 0.00 AC: 0 AN: 46048

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	4.4
DANN	Benign	0.82
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.23
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.17
Sift	Benign	0.51	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.58		Gain of disorder (P = 0.0084)
MVP		0.75
MPC		0.91
ClinPred		0.020	T
GERP RS		0.87
Varity_R		0.17
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs2042817718; hg19: chrX-71425931;