5-41143013-T-TGA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000065.5(C6):c.2624-8_2624-7insTC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000951 in 1,609,426 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: C6 NM_000065.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

Genes affected

C6 (HGNC:1339): (complement C6) This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]

LOC105374739 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-41143013-T-TGA is Benign according to our data. Variant chr5-41143013-T-TGA is described in ClinVar as [Benign]. Clinvar id is 1598827.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6	NM_000065.5	c.2624-8_2624-7insTC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000337836.10
LOC105374739	XR_001742650.2	n.887-18287_887-18286dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6	ENST00000337836.10	c.2624-8_2624-7insTC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000065.5	P1
C6	ENST00000263413.7	c.2624-8_2624-7insTC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P1
C6	ENST00000706654.1	n.791-8_791-7insTC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 23 AN: 151430 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000483

GnomAD3 exomes AF: 0.000305 AC: 74 AN: 242886 Hom.: 0 AF XY: 0.000198 AC XY: 26 AN XY: 131268

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00335

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000488

Gnomad NFE exome AF: 0.0000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000892 AC: 130 AN: 1457878 Hom.: 0 Cov.: 30 AF XY: 0.0000813 AC XY: 59 AN XY: 725386

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00172

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.0000370

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000152 AC: 23 AN: 151548 Hom.: 0 Cov.: 32 AF XY: 0.000203 AC XY: 15 AN XY: 74048

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.000185

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs752102682; hg19: chr5-41143115;