rs7710005

chr5-233457-A-Gchr5-233457-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004168.4(SDHA):c.896-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,610,802 control chromosomes in the GnomAD database, including 23,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6814 hom., cov: 33)
  • Exomes 𝑓: 0.14 (17149 hom.)
• Consequence: SDHA NM_004168.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.84

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-233457-A-G is Benign according to our data. Variant chr5-233457-A-G is described in ClinVar as [Benign]. Clinvar id is 259249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-233457-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHA	NM_004168.4	c.896-20A>G		intron_variant		ENST00000264932.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHA	ENST00000264932.11	c.896-20A>G		intron_variant		1	NM_004168.4	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36433 AN: 152102 Hom.: 6787 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.232

GnomAD3 exomes AF: 0.152 AC: 38298 AN: 251460 Hom.: 4442 AF XY: 0.143 AC XY: 19461 AN XY: 135900

Gnomad AFR exome AF: 0.542

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.0608

Gnomad SAS exome AF: 0.0905

Gnomad FIN exome AF: 0.0862

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.136 AC: 198638 AN: 1458582 Hom.: 17149 Cov.: 30 AF XY: 0.134 AC XY: 96959 AN XY: 725802

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.0480

Gnomad4 SAS exome AF: 0.0899

Gnomad4 FIN exome AF: 0.0884

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.240 AC: 36507 AN: 152220 Hom.: 6814 Cov.: 33 AF XY: 0.234 AC XY: 17416 AN XY: 74432

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0556

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.228

Alfa AF: 0.186 Hom.: 894

Bravo AF: 0.266

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 03, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Paragangliomas 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.029
Dann	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7710005; hg19: chr5-233572; COSMIC: COSV53765885; COSMIC: COSV53765885;