rs10252691

Positions:

• chr7-97169508-A-C
• chr7-97169508-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.175-11504A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,154 control chromosomes in the GnomAD database, including 899 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 0.11 (899 hom., cov: 33)
• Consequence: SDHAF3 NM_020186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHAF3	NM_020186.3	c.175-11504A>C		intron_variant		ENST00000432641.3	NP_064571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHAF3	ENST00000432641.3	c.175-11504A>C		intron_variant		1	NM_020186.3	ENSP00000414066	P1
SDHAF3	ENST00000360382.4	c.*48-11504A>C		intron_variant		2		ENSP00000353548
SDHAF3	ENST00000479853.1	n.139-11504A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16575 AN: 152036 Hom.: 897 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0909

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0657

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.109 AC: 16593 AN: 152154 Hom.: 899 Cov.: 33 AF XY: 0.109 AC XY: 8110 AN XY: 74398

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0957 Hom.: 380

Bravo AF: 0.109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.58

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: rs10252691; hg19: chr7-96798820;