rs12056091

chr7-97129359-G-Achr7-97129359-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020186.3(SDHAF3):c.174+11462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,996 control chromosomes in the GnomAD database, including 9,508 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9508 hom., cov: 32)
• Consequence: SDHAF3 NM_020186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

Genes affected

SDHAF3 (HGNC:21752): (succinate dehydrogenase complex assembly factor 3) Predicted to be involved in mitochondrial respiratory chain complex II assembly; regulation of gluconeogenesis; and succinate metabolic process. Predicted to be located in mitochondrial matrix. Predicted to be active in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHAF3	NM_020186.3	c.174+11462G>A		intron_variant		ENST00000432641.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHAF3	ENST00000432641.3	c.174+11462G>A		intron_variant		1	NM_020186.3	P1
SDHAF3	ENST00000360382.4	c.175-7029G>A		intron_variant		2
SDHAF3	ENST00000489852.1	n.197+11462G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53433 AN: 151878 Hom.: 9500 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.352 AC: 53465 AN: 151996 Hom.: 9508 Cov.: 32 AF XY: 0.355 AC XY: 26323 AN XY: 74250

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.381

Alfa AF: 0.356 Hom.: 18575

Bravo AF: 0.351

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	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: rs12056091; hg19: chr7-96758671;