rs12670377

Positions:

• chr7-97157313-C-A

Variant summary

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

The NM_020186.3(SDHAF3):​c.175-23699C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,050 control chromosomes in the GnomAD database, including 4,712 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 0.24 (4712 hom., cov: 32)
• Consequence: SDHAF3 NM_020186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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]

LOC107984034 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHAF3	NM_020186.3	c.175-23699C>A		intron_variant		ENST00000432641.3	NP_064571.1
LOC107984034	XR_001745291.1	n.280C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHAF3	ENST00000432641.3	c.175-23699C>A		intron_variant		1	NM_020186.3	ENSP00000414066	P1
SDHAF3	ENST00000360382.4	c.*47+20846C>A		intron_variant		2		ENSP00000353548
SDHAF3	ENST00000479853.1	n.138+14495C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37157 AN: 151932 Hom.: 4710 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.245 AC: 37178 AN: 152050 Hom.: 4712 Cov.: 32 AF XY: 0.247 AC XY: 18357 AN XY: 74322

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.262

Alfa AF: 0.254 Hom.: 8690

Bravo AF: 0.245

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.82

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: rs12670377; hg19: chr7-96786625;