9-97675579-G-C

Variant names:

• chr9-97675579-G-C
• NM_000380.4:c.682C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000380.4(XPA):​c.682C>G​(p.Arg228Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPA NM_000380.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

Genes affected

XPA (HGNC:12814): (XPA, DNA damage recognition and repair factor) This gene encodes a zinc finger protein plays a central role in nucleotide excision repair (NER), a specialized type of DNA repair. NER is responsible for repair of UV radiation-induced photoproducts and DNA adducts induced by chemical carcinogens and chemotherapeutic drugs. The encoded protein interacts with DNA and several NER proteins, acting as a scaffold to assemble the NER incision complex at sites of DNA damage. Mutations in this gene cause Xeroderma pigmentosum complementation group A (XP-A), an autosomal recessive skin disorder featuring hypersensitivity to sunlight and increased risk for skin cancer. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPA	NM_000380.4	c.682C>G	p.Arg228Gly	missense_variant	Exon 6 of 6	ENST00000375128.5	NP_000371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPA	ENST00000375128.5	c.682C>G	p.Arg228Gly	missense_variant	Exon 6 of 6	1	NM_000380.4	ENSP00000364270.5
XPA	ENST00000462523.5	n.*118C>G		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000433006.1
XPA	ENST00000485042.1	n.194C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
XPA	ENST00000462523.5	n.*118C>G		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000433006.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.24
Sift	Benign	0.14	T
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.71
MutPred		0.28		Loss of stability (P = 0.0567);
MVP		0.76
MPC		0.85
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.45
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-100437861;