10-119141097-G-A

Position:

• chr10-119141097-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_213649.2(SFXN4):​c.*145C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 584,390 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (21 hom.)
• Consequence: SFXN4 NM_213649.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-119141097-G-A is Benign according to our data. Variant chr10-119141097-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1188485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00556 (847/152222) while in subpopulation NFE AF= 0.00815 (554/68008). AF 95% confidence interval is 0.00758. There are 5 homozygotes in gnomad4. There are 374 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.*145C>T		3_prime_UTR_variant	14/14	ENST00000355697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7	c.*145C>T		3_prime_UTR_variant	14/14	1	NM_213649.2	P1
SFXN4	ENST00000484960.5	n.371C>T		non_coding_transcript_exon_variant	3/3	3
SFXN4	ENST00000490417.6	n.622C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00558 AC: 848 AN: 152104 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00815

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00666 AC: 2879 AN: 432168 Hom.: 21 Cov.: 5 AF XY: 0.00676 AC XY: 1565 AN XY: 231408

Gnomad4 AFR exome AF: 0.000651

Gnomad4 AMR exome AF: 0.00476

Gnomad4 ASJ exome AF: 0.0374

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00372

Gnomad4 FIN exome AF: 0.000933

Gnomad4 NFE exome AF: 0.00745

Gnomad4 OTH exome AF: 0.00829

GnomAD4 genome AF: 0.00556 AC: 847 AN: 152222 Hom.: 5 Cov.: 32 AF XY: 0.00503 AC XY: 374 AN XY: 74408

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00815

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00470 Hom.: 1

Bravo AF: 0.00566

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.66
DANN	Benign	0.46

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;