10-119141097-G-T

Variant names:

• chr10-119141097-G-T
• rs72832455
• NM_213649.2:c.*145C>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_213649.2(SFXN4):​c.*145C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 584,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: SFXN4 NM_213649.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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 -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00023 (35/152106) while in subpopulation NFE AF= 0.0005 (34/68016). AF 95% confidence interval is 0.000368. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.*145C>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000355697.7	NP_998814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN4	ENST00000355697	c.*145C>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_213649.2	ENSP00000347924.2
SFXN4	ENST00000484960.5	n.371C>A		non_coding_transcript_exon_variant	Exon 3 of 3	3
SFXN4	ENST00000490417.6	n.622C>A		non_coding_transcript_exon_variant	Exon 5 of 5	2
SFXN4	ENST00000461438.5	n.*159C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000250 AC: 108 AN: 432190 Hom.: 0 Cov.: 5 AF XY: 0.000255 AC XY: 59 AN XY: 231418

Gnomad4 AFR exome AF: 0.0000930

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000195

Gnomad4 FIN exome AF: 0.0000910

Gnomad4 NFE exome AF: 0.000368

Gnomad4 OTH exome AF: 0.0000842

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74280

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.59

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: rs72832455; hg19: chr10-120900609;