rs750358005

Variant names:

• chr16-13920199-A-C
• rs750358005
• NM_005236.3:c.34A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-13920199-A-C
• chr16-13920199-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005236.3(ERCC4):​c.34A>C​(p.Met12Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,792 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ERCC4 NM_005236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.98

Genes affected

ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

LOC105371093 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.34A>C	p.Met12Leu	missense_variant	Exon 1 of 11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.34A>C	p.Met12Leu	missense_variant	Exon 1 of 12		XP_011520726.1
LOC105371093	XR_007064999.1	n.82+6326T>G		intron_variant	Intron 1 of 2
LOC105371093	XR_007065000.1	n.82+6326T>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.34A>C	p.Met12Leu	missense_variant	Exon 1 of 11	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454792 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 724092

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.063
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.72	.;N
REVEL	Benign	0.20
Sift	Benign	0.067	.;T
Sift4G	Benign	0.69	T;T
Polyphen		0.27	.;B
Vest4		0.60
MutPred		0.35		Loss of catalytic residue at M12 (P = 0.0959);Loss of catalytic residue at M12 (P = 0.0959);
MVP		0.81
MPC		0.086
ClinPred		0.83	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.77
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs750358005; hg19: chr16-14014056;