10-101037017-C-T

Variant names:

• chr10-101037017-C-T
• rs2275383
• NM_030971.6:c.594-59C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030971.6(SFXN3):​c.594-59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,599,236 control chromosomes in the GnomAD database, including 126,319 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 0.31 (8707 hom., cov: 31)
  • Exomes 𝑓: 0.40 (117612 hom.)
• Consequence: SFXN3 NM_030971.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• Publications: 8 publications found

Genes affected

SFXN3 (HGNC:16087): (sideroflexin 3) Enables serine transmembrane transporter activity. Involved in serine import into mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN3	NM_030971.6	c.594-59C>T		intron_variant	Intron 7 of 11	ENST00000393459.6	NP_112233.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN3	ENST00000393459.6	c.594-59C>T		intron_variant	Intron 7 of 11	5	NM_030971.6	ENSP00000377103.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46949 AN: 151826 Hom.: 8709 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.398 AC: 576190 AN: 1447292 Hom.: 117612 Cov.: 36 AF XY: 0.398 AC XY: 286290 AN XY: 718486

African (AFR) AF: 0.0913 AC: 3035 AN: 33260

American (AMR) AF: 0.295 AC: 12771 AN: 43316

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 11896 AN: 25512

East Asian (EAS) AF: 0.409 AC: 16121 AN: 39398

South Asian (SAS) AF: 0.364 AC: 30968 AN: 85120

European-Finnish (FIN) AF: 0.302 AC: 15359 AN: 50934

Middle Eastern (MID) AF: 0.372 AC: 1882 AN: 5058

European-Non Finnish (NFE) AF: 0.417 AC: 460491 AN: 1104938

Other (OTH) AF: 0.396 AC: 23667 AN: 59756

GnomAD4 genome AF: 0.309 AC: 46930 AN: 151944 Hom.: 8707 Cov.: 31 AF XY: 0.306 AC XY: 22738 AN XY: 74260

African (AFR) AF: 0.102 AC: 4235 AN: 41450

American (AMR) AF: 0.335 AC: 5116 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1571 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2258 AN: 5154

South Asian (SAS) AF: 0.356 AC: 1710 AN: 4804

European-Finnish (FIN) AF: 0.293 AC: 3097 AN: 10560

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27658 AN: 67914

Other (OTH) AF: 0.344 AC: 724 AN: 2106

Alfa AF: 0.329 Hom.: 3463

Bravo AF: 0.304

Asia WGS AF: 0.389 AC: 1350 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.027
DANN	Benign	0.55
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2275383; hg19: chr10-102796774; COSMIC: COSV56521322; COSMIC: COSV56521322;