rs12671685

Positions:

• chr7-97176817-A-G
• chr7-97176817-A-T

Variant summary

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

The NM_020186.3(SDHAF3):​c.175-4195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 151,680 control chromosomes in the GnomAD database, including 2,592 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 0.17 (2592 hom., cov: 32)
• Consequence: SDHAF3 NM_020186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHAF3	NM_020186.3	c.175-4195A>G		intron_variant		ENST00000432641.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHAF3	ENST00000432641.3	c.175-4195A>G		intron_variant		1	NM_020186.3	P1
SDHAF3	ENST00000360382.4	c.*48-4195A>G		intron_variant		2
SDHAF3	ENST00000479853.1	n.139-4195A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26359 AN: 151564 Hom.: 2586 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.174 AC: 26395 AN: 151680 Hom.: 2592 Cov.: 32 AF XY: 0.179 AC XY: 13254 AN XY: 74174

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.183

Alfa AF: 0.135 Hom.: 688

Bravo AF: 0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.90

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: rs12671685; hg19: chr7-96806129;