7-97181085-C-T

Variant names:

• chr7-97181085-C-T
• rs34146273
• NM_020186.3:c.248C>T

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.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. 14/19 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 6 publications found

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]

LOC124901704 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003202647).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 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 GnomAdExome4. There are 396 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF3	NM_020186.3	c.248C>T	p.Thr83Ile	missense_variant	Exon 2 of 2	ENST00000432641.3	NP_064571.1
LOC124901704	XR_007060445.1	n.132-736G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHAF3	ENST00000432641.3	c.248C>T	p.Thr83Ile	missense_variant	Exon 2 of 2	1	NM_020186.3	ENSP00000414066.2
SDHAF3	ENST00000479853.1	n.212C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
SDHAF3	ENST00000360382.4	c.*121C>T		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000353548.4

Frequencies

GnomAD3 genomes AF: 0.00452 AC: 687 AN: 152138 Hom.: 8 Cov.: 32

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

GnomAD2 exomes AF: 0.00121 AC: 304 AN: 251356 AF XY: 0.000950

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 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.: 7 Cov.: 30 AF XY: 0.000545 AC XY: 396 AN XY: 727156

African (AFR) AF: 0.0183 AC: 611 AN: 33476

American (AMR) AF: 0.000470 AC: 21 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86246

European-Finnish (FIN) AF: 0.000580 AC: 31 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.000130 AC: 144 AN: 1111930

Other (OTH) AF: 0.000994 AC: 60 AN: 60386

GnomAD4 genome AF: 0.00451 AC: 687 AN: 152256 Hom.: 8 Cov.: 32 AF XY: 0.00427 AC XY: 318 AN XY: 74464

African (AFR) AF: 0.0156 AC: 647 AN: 41540

American (AMR) AF: 0.000916 AC: 14 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00163 Hom.: 6

Bravo AF: 0.00519

ESP6500AA AF: 0.0138 AC: 61

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00138 AC: 168

Asia WGS AF: 0.000577 AC: 2 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	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.1
DANN	Benign	0.95
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.31
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.029
Sift	Benign	0.29	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.029
MVP		0.048
MPC		0.088
ClinPred		0.0014	T
GERP RS		0.68
Varity_R		0.036
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs34146273; hg19: chr7-96810397;