rs376929555

Variant names:

• chr10-119146228-G-A
• rs376929555
• NM_213649.2:c.936+8C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-119146228-G-A
• chr10-119146228-G-C
• chr10-119146228-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_213649.2(SFXN4):​c.936+8C>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 0.0000275 in 1,453,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: SFXN4 NM_213649.2 splice_region, intron
• Scores: Splicing: ADA: 0.00005827
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-119146228-G-A is Benign according to our data. Variant chr10-119146228-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 794063.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.936+8C>T		splice_region_variant, intron_variant	Intron 13 of 13	ENST00000355697.7	NP_998814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN4	ENST00000355697.7	c.936+8C>T		splice_region_variant, intron_variant	Intron 13 of 13	1	NM_213649.2	ENSP00000347924.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000576 AC: 14 AN: 243070 AF XY: 0.0000610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000723

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000340

GnomAD4 exome AF: 0.0000269 AC: 35 AN: 1301498 Hom.: 0 Cov.: 18 AF XY: 0.0000351 AC XY: 23 AN XY: 654922

African (AFR) AF: 0.00 AC: 0 AN: 30066

American (AMR) AF: 0.00 AC: 0 AN: 42254

Ashkenazi Jewish (ASJ) AF: 0.000685 AC: 17 AN: 24804

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38834

South Asian (SAS) AF: 0.00 AC: 0 AN: 80104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5458

European-Non Finnish (NFE) AF: 0.0000134 AC: 13 AN: 971610

Other (OTH) AF: 0.0000725 AC: 4 AN: 55152

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000762 Hom.: 0

Bravo AF: 0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.23
PhyloP100		-0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000058
dbscSNV1_RF	Benign	0.0080
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: rs376929555; hg19: chr10-120905740;