NM_213649.2:c.937-148_937-146delAAA

Variant names:

• chr10-119141464-ATTT-A
• rs34287145
• NM_213649.2:c.937-148_937-146delAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_213649.2(SFXN4):​c.937-148_937-146delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 322,664 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0034 (0 hom.)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00344 (610/177450) while in subpopulation EAS AF= 0.00408 (48/11776). AF 95% confidence interval is 0.00328. There are 0 homozygotes in gnomad4_exome. There are 319 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.937-148_937-146delAAA		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.937-148_937-146delAAA		intron_variant	Intron 13 of 13	1	NM_213649.2	ENSP00000347924.2
SFXN4	ENST00000461438.5	n.966-148_966-146delAAA		intron_variant	Intron 14 of 14	5
SFXN4	ENST00000484960.5	n.149-148_149-146delAAA		intron_variant	Intron 2 of 2	3
SFXN4	ENST00000490417.6	n.400-148_400-146delAAA		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.000165 AC: 24 AN: 145214 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000869

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000269

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00344 AC: 610 AN: 177450 Hom.: 0 AF XY: 0.00335 AC XY: 319 AN XY: 95182

Gnomad4 AFR exome AF: 0.00110

Gnomad4 AMR exome AF: 0.00350

Gnomad4 ASJ exome AF: 0.00664

Gnomad4 EAS exome AF: 0.00408

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.00314

Gnomad4 NFE exome AF: 0.00357

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.000165 AC: 24 AN: 145214 Hom.: 0 Cov.: 0 AF XY: 0.000157 AC XY: 11 AN XY: 70168

Gnomad4 AFR AF: 0.0000776

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000869

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000269

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00154 Hom.: 35

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;