10-119145910-T-C

Position:

• chr10-119145910-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_213649.2(SFXN4):​c.936+326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,992 control chromosomes in the GnomAD database, including 7,893 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7893 hom., cov: 31)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 10-119145910-T-C is Benign according to our data. Variant chr10-119145910-T-C is described in ClinVar as [Benign]. Clinvar id is 683836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.936+326A>G		intron_variant		ENST00000355697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7	c.936+326A>G		intron_variant		1	NM_213649.2	P1
SFXN4	ENST00000461438.5	n.965+326A>G		intron_variant, non_coding_transcript_variant		5
SFXN4	ENST00000484960.5	n.148+1865A>G		intron_variant, non_coding_transcript_variant		3
SFXN4	ENST00000490417.6	n.399+326A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47112 AN: 151874 Hom.: 7897 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47121 AN: 151992 Hom.: 7893 Cov.: 31 AF XY: 0.317 AC XY: 23540 AN XY: 74302

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.322

Alfa AF: 0.350 Hom.: 1224

Bravo AF: 0.291

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.8
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs12411420; hg19: chr10-120905422;