1-56867620-G-T

Variant names:

• chr1-56867620-G-T
• rs201955480
• NM_000562.3:c.89G>T

Variant summary

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

The NM_000562.3(C8A):​c.89G>T​(p.Arg30Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C8A NM_000562.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

Genes affected

C8A (HGNC:1352): (complement C8 alpha chain) C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency. [provided by RefSeq, Nov 2008]

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, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8A	NM_000562.3	c.89G>T	p.Arg30Leu	missense_variant	Exon 2 of 11	ENST00000361249.4	NP_000553.1
C8A	XM_017002234.2	c.89G>T	p.Arg30Leu	missense_variant	Exon 2 of 8		XP_016857723.1
C8A	XM_011542079.3	c.89G>T	p.Arg30Leu	missense_variant	Exon 2 of 8		XP_011540381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8A	ENST00000361249.4	c.89G>T	p.Arg30Leu	missense_variant	Exon 2 of 11	1	NM_000562.3	ENSP00000354458.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460870 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726770

Gnomad4 AFR exome AF: 0.00

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.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.47
Sift	Benign	0.076	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.51		Loss of MoRF binding (P = 0.0107);
MVP		0.91
MPC		0.082
ClinPred		0.85	D
GERP RS		5.1
Varity_R		0.25
gMVP		0.65

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: rs201955480; hg19: chr1-57333293;