rs759695823

Variant names:

• chr2-127257653-C-A
• rs759695823
• NM_000122.2:c.2292G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-127257653-C-A
• chr2-127257653-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000122.2(ERCC3):​c.2292G>T​(p.Ser764Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S764S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERCC3 NM_000122.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.63
• Publications: 0 publications found

Genes affected

ERCC3 (HGNC:3435): (ERCC excision repair 3, TFIIH core complex helicase subunit) This gene encodes an ATP-dependent DNA helicase that functions in nucleotide excision repair. The encoded protein is a subunit of basal transcription factor 2 (TFIIH) and, therefore, also functions in class II transcription. Mutations in this gene are associated with Xeroderma pigmentosum B, Cockayne's syndrome, and trichothiodystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ERCC3 Gene-Disease associations (from GenCC):

• trichothiodystrophy 2, photosensitive

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• xeroderma pigmentosum group B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen
• trichothiodystrophy 1, photosensitive

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• xeroderma pigmentosum-Cockayne syndrome complex

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-4.63 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000122.2. 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
	ERCC3	NM_000122.2	MANE Select	c.2292G>T	p.Ser764Ser	synonymous	Exon 15 of 15	NP_000113.1	P19447
	ERCC3	NM_001303416.2		c.2100G>T	p.Ser700Ser	synonymous	Exon 15 of 15	NP_001290345.1
	ERCC3	NM_001303418.2		c.2100G>T	p.Ser700Ser	synonymous	Exon 15 of 15	NP_001290347.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC3	ENST00000285398.7	TSL:1 MANE Select	c.2292G>T	p.Ser764Ser	synonymous	Exon 15 of 15	ENSP00000285398.2	P19447
	ERCC3	ENST00000647169.1		c.2367G>T	p.Ser789Ser	synonymous	Exon 16 of 16	ENSP00000495619.1	A0A2R8Y6W8
	ERCC3	ENST00000918332.1		c.2343G>T	p.Ser781Ser	synonymous	Exon 15 of 15	ENSP00000588391.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.069
DANN	Benign	0.48
PhyloP100		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	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: rs759695823; hg19: chr2-128015229;