rs3740558

Variant names:

• chr10-119159667-G-A
• rs3740558
• NM_213649.2:c.360+61C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-119159667-G-A
• chr10-119159667-G-C
• chr10-119159667-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213649.2(SFXN4):​c.360+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,558,406 control chromosomes in the GnomAD database, including 197,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18002 hom., cov: 31)
  • Exomes 𝑓: 0.50 (179039 hom.)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27
• Publications: 19 publications found

Genes affected

SFXN4 (HGNC:16088): (sideroflexin 4) This gene encodes a member of the sideroflexin family. The encoded protein is a transmembrane protein of the inner mitochondrial membrane, and is required for mitochondrial respiratory homeostasis and erythropoiesis. Mutations in this gene are associated with mitochondriopathy and macrocytic anemia. Alternatively spliced transcript variants have been found in this gene. [provided by RefSeq, Jan 2014]

SFXN4 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-119159667-G-A is Benign according to our data. Variant chr10-119159667-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.360+61C>T		intron_variant	Intron 6 of 13	ENST00000355697.7	NP_998814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN4	ENST00000355697.7	c.360+61C>T		intron_variant	Intron 6 of 13	1	NM_213649.2	ENSP00000347924.2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73341 AN: 151806 Hom.: 17985 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.502 AC: 706418 AN: 1406482 Hom.: 179039 AF XY: 0.500 AC XY: 351604 AN XY: 702924

African (AFR) AF: 0.428 AC: 13829 AN: 32326

American (AMR) AF: 0.463 AC: 20660 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 14333 AN: 25840

East Asian (EAS) AF: 0.693 AC: 27348 AN: 39468

South Asian (SAS) AF: 0.445 AC: 37811 AN: 85058

European-Finnish (FIN) AF: 0.439 AC: 23436 AN: 53344

Middle Eastern (MID) AF: 0.463 AC: 2627 AN: 5674

European-Non Finnish (NFE) AF: 0.505 AC: 536352 AN: 1061566

Other (OTH) AF: 0.512 AC: 30022 AN: 58582

GnomAD4 genome AF: 0.483 AC: 73395 AN: 151924 Hom.: 18002 Cov.: 31 AF XY: 0.481 AC XY: 35699 AN XY: 74244

African (AFR) AF: 0.438 AC: 18146 AN: 41422

American (AMR) AF: 0.481 AC: 7343 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3696 AN: 5140

South Asian (SAS) AF: 0.452 AC: 2170 AN: 4804

European-Finnish (FIN) AF: 0.444 AC: 4695 AN: 10564

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33829 AN: 67958

Other (OTH) AF: 0.486 AC: 1027 AN: 2112

Alfa AF: 0.473 Hom.: 3066

Bravo AF: 0.487

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.67
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3740558; hg19: chr10-120919179;