Variant rs62624461 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.69

Variant links:

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]

SDHAF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHAF3	NM_020186.3 linkuse as main transcript	c.157T>C	p.Phe53Leu	missense_variant	1/2	ENST00000432641.3	NP_064571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SDHAF3	ENST00000432641.3 linkuse as main transcript	c.157T>C	p.Phe53Leu	missense_variant	1/2	1	NM_020186.3	ENSP00000414066	P1
SDHAF3	ENST00000360382.4 linkuse as main transcript	c.157T>C	p.Phe53Leu	missense_variant	1/3	2		ENSP00000353548
SDHAF3	ENST00000489852.1 linkuse as main transcript	n.180T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2696

AN:

152206

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0202

AC:

5026

AN:

248826

Hom.:

AF XY:

0.0217

AC XY:

2926

AN XY:

134680

show subpopulations

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 SAS exome

AF:

0.0286

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.:

AF XY:

0.0251

AC XY:

18232

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00364

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.0243

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0295

Gnomad4 FIN exome

AF:

0.0237

Gnomad4 NFE exome

AF:

0.0266

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.0177

AC:

2693

AN:

152324

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1306

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00495

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0257

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0236

Hom.:

Bravo

AF:

0.0163

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0280

AC:

108

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.0249

AC:

214

ExAC

AF:

0.0208

AC:

2529

Asia WGS

AF:

0.0120

AC:

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

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

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

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over