chr10-119141464-A-AT

Variant names:

• chr10-119141464-A-AT
• rs34287145
• NM_213649.2:c.937-146dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_213649.2(SFXN4):​c.937-146dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 324,518 control chromosomes in the GnomAD database, including 16 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0094 (15 hom., cov: 0)
  • Exomes 𝑓: 0.00090 (1 hom.)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00939 (1364/145304) while in subpopulation AFR AF= 0.0327 (1266/38738). AF 95% confidence interval is 0.0312. There are 15 homozygotes in gnomad4. There are 624 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.937-146dupA		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.937-146_937-145insA		intron_variant	Intron 13 of 13	1	NM_213649.2	ENSP00000347924.2
SFXN4	ENST00000461438.5	n.966-146_966-145insA		intron_variant	Intron 14 of 14	5
SFXN4	ENST00000484960.5	n.149-146_149-145insA		intron_variant	Intron 2 of 2	3
SFXN4	ENST00000490417.6	n.400-146_400-145insA		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.00932 AC: 1353 AN: 145210 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00515

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.000179

Gnomad OTH AF: 0.00499

GnomAD4 exome AF: 0.000904 AC: 162 AN: 179214 Hom.: 1 AF XY: 0.000811 AC XY: 78 AN XY: 96162

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.00371

GnomAD4 genome AF: 0.00939 AC: 1364 AN: 145304 Hom.: 15 Cov.: 0 AF XY: 0.00888 AC XY: 624 AN XY: 70272

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.00514

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000179

Gnomad4 OTH AF: 0.00494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs34287145; hg19: chr10-120900976;