chr7-97117880-T-C

Variant names:

• chr7-97117880-T-C
• rs62624461
• NM_020186.3:c.157T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020186.3(SDHAF3):​c.157T>C​(p.Phe53Leu) variant causes a missense change. The variant allele was found at a frequency of 0.024 in 1,614,092 control chromosomes in the GnomAD database, including 520 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 0.018 (35 hom., cov: 33)
  • Exomes 𝑓: 0.025 (485 hom.)
• Consequence: SDHAF3 NM_020186.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.69

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 (MetaRNN=0.008035541).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0177 (2693/152324) while in subpopulation NFE AF = 0.0262 (1781/68020). AF 95% confidence interval is 0.0252. There are 35 homozygotes in GnomAd4. There are 1306 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF3	NM_020186.3	c.157T>C	p.Phe53Leu	missense_variant	Exon 1 of 2	ENST00000432641.3	NP_064571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHAF3	ENST00000432641.3	c.157T>C	p.Phe53Leu	missense_variant	Exon 1 of 2	1	NM_020186.3	ENSP00000414066.2
SDHAF3	ENST00000360382.4	c.157T>C	p.Phe53Leu	missense_variant	Exon 1 of 3	2		ENSP00000353548.4
SDHAF3	ENST00000489852.1	n.180T>C		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2696 AN: 152206 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0202 AC: 5026 AN: 248826 AF XY: 0.0217

Gnomad AFR exome AF: 0.00554

Gnomad AMR exome AF: 0.00914

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0227

Gnomad NFE exome AF: 0.0261

Gnomad OTH exome AF: 0.0190

GnomAD4 exome AF: 0.0246 AC: 36028 AN: 1461768 Hom.: 485 Cov.: 30 AF XY: 0.0251 AC XY: 18232 AN XY: 727168

Gnomad4 AFR exome AF: 0.00364 AC: 122 AN: 33476

Gnomad4 AMR exome AF: 0.0102 AC: 454 AN: 44716

Gnomad4 ASJ exome AF: 0.0243 AC: 634 AN: 26120

Gnomad4 EAS exome AF: 0.000126 AC: 5 AN: 39700

Gnomad4 SAS exome AF: 0.0295 AC: 2544 AN: 86256

Gnomad4 FIN exome AF: 0.0237 AC: 1267 AN: 53408

Gnomad4 NFE exome AF: 0.0266 AC: 29542 AN: 1111932

Gnomad4 Remaining exome AF: 0.0229 AC: 1384 AN: 60392

GnomAD4 genome AF: 0.0177 AC: 2693 AN: 152324 Hom.: 35 Cov.: 33 AF XY: 0.0175 AC XY: 1306 AN XY: 74490

Gnomad4 AFR AF: 0.00495 AC: 0.00495383 AN: 0.00495383

Gnomad4 AMR AF: 0.0131 AC: 0.0130702 AN: 0.0130702

Gnomad4 ASJ AF: 0.0271 AC: 0.0270893 AN: 0.0270893

Gnomad4 EAS AF: 0.000386 AC: 0.00038625 AN: 0.00038625

Gnomad4 SAS AF: 0.0257 AC: 0.0256942 AN: 0.0256942

Gnomad4 FIN AF: 0.0218 AC: 0.0218332 AN: 0.0218332

Gnomad4 NFE AF: 0.0262 AC: 0.0261835 AN: 0.0261835

Gnomad4 OTH AF: 0.0156 AC: 0.015625 AN: 0.015625

Alfa AF: 0.0233 Hom.: 116

Bravo AF: 0.0163

TwinsUK AF: 0.0227 AC: 84

ALSPAC AF: 0.0280 AC: 108

ESP6500AA AF: 0.00635 AC: 28

ESP6500EA AF: 0.0249 AC: 214

ExAC AF: 0.0208 AC: 2529

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0209

EpiControl AF: 0.0220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.0080	T;T
MetaSVM	Benign	-0.73	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.076	T;T
Polyphen		0.78	P;.
Vest4		0.55
MutPred		0.91		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MPC		0.49
ClinPred		0.094	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.51
Mutation Taster		=55/45	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

Publications

LitVar

Other links and lift over

dbSNP: rs62624461; hg19: chr7-96747192;