rs2275111

Variant names:

• chr10-119157933-G-A
• rs2275111
• NM_213649.2:c.415-6C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-119157933-G-A
• chr10-119157933-G-C
• chr10-119157933-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.415-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,613,640 control chromosomes in the GnomAD database, including 203,917 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18105 hom., cov: 34)
  • Exomes 𝑓: 0.50 (185812 hom.)
• Consequence: SFXN4 NM_213649.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002648
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.19
• Publications: 31 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-119157933-G-A is Benign according to our data. Variant chr10-119157933-G-A is described in ClinVar as Benign. ClinVar VariationId is 380007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213649.2. 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
	SFXN4	NM_213649.2	MANE Select	c.415-6C>T		splice_region intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.433-6C>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN4	ENST00000355697.7	TSL:1 MANE Select	c.415-6C>T		splice_region intron	N/A	ENSP00000347924.2	Q6P4A7-1
	SFXN4	ENST00000955059.1		c.415-6C>T		splice_region intron	N/A	ENSP00000625118.1
	SFXN4	ENST00000369131.8	TSL:5	c.67-6C>T		splice_region intron	N/A	ENSP00000358127.4	B1AMV7

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73617 AN: 152032 Hom.: 18089 Cov.: 34

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.488

GnomAD2 exomes AF: 0.499 AC: 125461 AN: 251420 AF XY: 0.497

Gnomad AFR exome AF: 0.442

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.728

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.502 AC: 733778 AN: 1461490 Hom.: 185812 Cov.: 50 AF XY: 0.500 AC XY: 363626 AN XY: 727064

African (AFR) AF: 0.432 AC: 14477 AN: 33474

American (AMR) AF: 0.466 AC: 20831 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 14500 AN: 26132

East Asian (EAS) AF: 0.692 AC: 27463 AN: 39700

South Asian (SAS) AF: 0.444 AC: 38329 AN: 86242

European-Finnish (FIN) AF: 0.439 AC: 23448 AN: 53414

Middle Eastern (MID) AF: 0.462 AC: 2667 AN: 5768

European-Non Finnish (NFE) AF: 0.505 AC: 561129 AN: 1111654

Other (OTH) AF: 0.512 AC: 30934 AN: 60388

GnomAD4 genome AF: 0.484 AC: 73672 AN: 152150 Hom.: 18105 Cov.: 34 AF XY: 0.482 AC XY: 35863 AN XY: 74386

African (AFR) AF: 0.442 AC: 18337 AN: 41482

American (AMR) AF: 0.482 AC: 7368 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3719 AN: 5184

South Asian (SAS) AF: 0.452 AC: 2182 AN: 4828

European-Finnish (FIN) AF: 0.445 AC: 4711 AN: 10580

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33836 AN: 68014

Other (OTH) AF: 0.489 AC: 1032 AN: 2112

Alfa AF: 0.498 Hom.: 86488

Bravo AF: 0.489

Asia WGS AF: 0.548 AC: 1903 AN: 3478

EpiCase AF: 0.502

EpiControl AF: 0.502

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.36
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0020
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: rs2275111; hg19: chr10-120917445; COSMIC: COSV57460793; COSMIC: COSV57460793;