ERCC3 p.Arg425Arg

Variant names:

• chr2-127286769-C-C
• NM_000122.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-127286770--
• chr2-127286770-T-A
• chr2-127286770-T-G
• chr2-127286770-T-C
• chr2-127286772-G-T
• chr2-127286770-TCG-CCT

Variant summary

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

The NM_000122.2(ERCC3):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERCC3 NM_000122.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• 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), ClinGen, Genomics England PanelApp, G2P
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 8 of 15	NP_000113.1	P19447
	ERCC3	NM_001303416.2		c.		exon_region	Exon 8 of 15	NP_001290345.1
	ERCC3	NM_001303418.2		c.		exon_region	Exon 8 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.		exon_region	Exon 8 of 15	ENSP00000285398.2	P19447
	ERCC3	ENST00000494464.5	TSL:1	n.		exon_region	Exon 7 of 7
	ERCC3	ENST00000647169.1		c.		exon_region	Exon 8 of 16	ENSP00000495619.1	A0A2R8Y6W8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-128044345;