chr7-97181173-T-C

Variant names:

• chr7-97181173-T-C
• rs10266441
• NM_020186.3:c.336T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788
• Publications: 1 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020186.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHAF3	NM_020186.3	MANE Select	c.336T>C	p.Asn112Asn	synonymous	Exon 2 of 2	NP_064571.1	Q9NRP4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHAF3	ENST00000432641.3	TSL:1 MANE Select	c.336T>C	p.Asn112Asn	synonymous	Exon 2 of 2	ENSP00000414066.2	Q9NRP4
	SDHAF3	ENST00000360382.4	TSL:2	c.*209T>C		3_prime_UTR	Exon 3 of 3	ENSP00000353548.4	F8W9V1
	SDHAF3	ENST00000479853.1	TSL:2	n.300T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4217 AN: 152142 Hom.: 187 Cov.: 32

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

GnomAD2 exomes AF: 0.00710 AC: 1783 AN: 251136 AF XY: 0.00538

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 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.: 30 AF XY: 0.00248 AC XY: 1803 AN XY: 727088

African (AFR) AF: 0.0982 AC: 3287 AN: 33470

American (AMR) AF: 0.00559 AC: 250 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26120

East Asian (EAS) AF: 0.00292 AC: 116 AN: 39662

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86224

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5764

European-Non Finnish (NFE) AF: 0.000158 AC: 176 AN: 1111892

Other (OTH) AF: 0.00623 AC: 376 AN: 60380

GnomAD4 genome AF: 0.0277 AC: 4223 AN: 152260 Hom.: 187 Cov.: 32 AF XY: 0.0271 AC XY: 2018 AN XY: 74466

African (AFR) AF: 0.0965 AC: 4007 AN: 41528

American (AMR) AF: 0.00896 AC: 137 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68008

Other (OTH) AF: 0.0165 AC: 35 AN: 2116

Alfa AF: 0.00921 Hom.: 88

Bravo AF: 0.0316

Asia WGS AF: 0.00404 AC: 14 AN: 3476

EpiCase AF: 0.00

EpiControl AF: 0.000534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		-0.79
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs10266441; hg19: chr7-96810485;