chr7-97127745-T-C

Position:

• chr7-97127745-T-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+9848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,062 control chromosomes in the GnomAD database, including 5,383 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 0.25 (5383 hom., cov: 31)
• Consequence: SDHAF3 NM_020186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHAF3	NM_020186.3	c.174+9848T>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.174+9848T>C		intron_variant		1	NM_020186.3	ENSP00000414066	P1
SDHAF3	ENST00000360382.4	c.175-8643T>C		intron_variant		2		ENSP00000353548
SDHAF3	ENST00000489852.1	n.197+9848T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38588 AN: 151944 Hom.: 5381 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.254 AC: 38594 AN: 152062 Hom.: 5383 Cov.: 31 AF XY: 0.254 AC XY: 18846 AN XY: 74322

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.261

Alfa AF: 0.296 Hom.: 9441

Bravo AF: 0.241

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.80

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: rs4398831; hg19: chr7-96757057;