NM_020186.3:c.175-9323G>T

Variant names:

• chr7-97171689-G-T
• rs10499936
• NM_020186.3:c.175-9323G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020186.3(SDHAF3):​c.175-9323G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,092 control chromosomes in the GnomAD database, including 66,076 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 0.93 (66076 hom., cov: 31)
• Consequence: SDHAF3 NM_020186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF3	NM_020186.3	c.175-9323G>T		intron_variant	Intron 1 of 1	ENST00000432641.3	NP_064571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHAF3	ENST00000432641.3	c.175-9323G>T		intron_variant	Intron 1 of 1	1	NM_020186.3	ENSP00000414066.2
SDHAF3	ENST00000360382.4	c.*48-9323G>T		intron_variant	Intron 2 of 2	2		ENSP00000353548.4
SDHAF3	ENST00000479853.1	n.139-9323G>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141165 AN: 151974 Hom.: 66045 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.929 AC: 141252 AN: 152092 Hom.: 66076 Cov.: 31 AF XY: 0.924 AC XY: 68702 AN XY: 74336

African (AFR) AF: 0.863 AC: 35810 AN: 41484

American (AMR) AF: 0.847 AC: 12923 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3450 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3661 AN: 5170

South Asian (SAS) AF: 0.898 AC: 4326 AN: 4820

European-Finnish (FIN) AF: 0.987 AC: 10469 AN: 10608

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67447 AN: 67962

Other (OTH) AF: 0.932 AC: 1964 AN: 2108

Alfa AF: 0.968 Hom.: 169222

Bravo AF: 0.914

Asia WGS AF: 0.792 AC: 2730 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.31
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10499936; hg19: chr7-96801001;