Genetic Variant SDHAF3:p.Asn112Asn (chr7-97181173-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020186.3(SDHAF3):c.336T>C(p.Asn112Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00525 in 1,613,880 control chromosomes in the GnomAD database, including 371 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 0.028 ( 187 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 184 hom. )

Consequence

SDHAF3
NM_020186.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.788

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-0.788 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF3	NM_020186.3 link	c.336T>C	p.Asn112Asn	synonymous_variant	Exon 2 of 2	ENST00000432641.3	NP_064571.1	Q9NRP4
LOC124901704	XR_007060445.1 link	n.132-824A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDHAF3	ENST00000432641.3 link	c.336T>C	p.Asn112Asn	synonymous_variant	Exon 2 of 2	1	NM_020186.3	ENSP00000414066.2	Q9NRP4
SDHAF3	ENST00000360382.4 link	c.*209T>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000353548.4	F8W9V1
SDHAF3	ENST00000479853.1 link	n.300T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4217

AN:

152142

Hom.:

187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00710

AC:

1783

AN:

251136

Hom.:

AF XY:

0.00538

AC XY:

730

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0935

Gnomad AMR exome

AF:

0.00461

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00256

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00291

AC:

4251

AN:

1461620

Hom.:

184

Cov.:

AF XY:

0.00248

AC XY:

1803

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.0982

Gnomad4 AMR exome

AF:

0.00559

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00292

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.0277

AC:

4223

AN:

152260

Hom.:

187

Cov.:

AF XY:

0.0271

AC XY:

2018

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0965

Gnomad4 AMR

AF:

0.00896

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.00613

Hom.:

Bravo

AF:

0.0316

Asia WGS

AF:

0.00404

AC:

AN:

3476

EpiCase

AF:

0.00

EpiControl

AF:

0.000534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

DANN

Benign

0.28

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