Variant rs34146273 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.248C>T(p.Thr83Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000968 in 1,613,984 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0045 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 7 hom. )

Consequence

SDHAF3
NM_020186.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.309

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:

LOC124901704 (HGNC:):

LOC124901704 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=0.003202647).

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000599 (876/1461728) while in subpopulation AFR AF= 0.0183 (611/33476). AF 95% confidence interval is 0.0171. There are 7 homozygotes in gnomad4_exome. There are 396 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHAF3	NM_020186.3 linkuse as main transcript	c.248C>T	p.Thr83Ile	missense_variant	2/2	ENST00000432641.3
LOC124901704	XR_007060445.1 linkuse as main transcript	n.132-736G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SDHAF3	ENST00000432641.3 linkuse as main transcript	c.248C>T	p.Thr83Ile	missense_variant	2/2	1	NM_020186.3	P1
SDHAF3	ENST00000360382.4 linkuse as main transcript	c.*121C>T		3_prime_UTR_variant	3/3	2
SDHAF3	ENST00000479853.1 linkuse as main transcript	n.212C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00452

AC:

687

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00121

AC:

304

AN:

251356

Hom.:

AF XY:

0.000950

AC XY:

129

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000599

AC:

876

AN:

1461728

Hom.:

Cov.:

AF XY:

0.000545

AC XY:

396

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.00451

AC:

687

AN:

152256

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000838

Hom.:

Bravo

AF:

0.00519

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00138

AC:

168

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.1

DANN

Benign

0.95

DEOGEN2

Benign

0.023

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

REVEL

Benign

0.029

Sift

Benign

0.29

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.029

MVP

0.048

MPC

0.088

ClinPred

0.0014

GERP RS

0.68

Varity_R

0.036

gMVP

0.16

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