5-228163-CTT-CTTT

Position:

• chr5-228163-CTT-CTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_004168.4(SDHA):​c.622-13dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 151,316 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: 𝑓 0.00018 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SDHA NM_004168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

Genes affected

SDHA (HGNC:10680): (succinate dehydrogenase complex flavoprotein subunit A) This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000178 (27/151316) while in subpopulation EAS AF= 0.00447 (23/5146). AF 95% confidence interval is 0.00305. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHA	NM_004168.4	c.622-13dup		intron_variant		ENST00000264932.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHA	ENST00000264932.11	c.622-13dup		intron_variant		1	NM_004168.4	P1

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 27 AN: 151202 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00446

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000484

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000207 AC: 299 AN: 1443312 Hom.: 0 Cov.: 29 AF XY: 0.000205 AC XY: 147 AN XY: 718494

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000450

Gnomad4 ASJ exome AF: 0.0000773

Gnomad4 EAS exome AF: 0.00297

Gnomad4 SAS exome AF: 0.0000583

Gnomad4 FIN exome AF: 0.000344

Gnomad4 NFE exome AF: 0.000124

Gnomad4 OTH exome AF: 0.000302

GnomAD4 genome AF: 0.000178 AC: 27 AN: 151316 Hom.: 0 Cov.: 26 AF XY: 0.000203 AC XY: 15 AN XY: 73922

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00447

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.000480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3835068; hg19: chr5-228278;