chr10-119146333-T-C

Variant names:

• chr10-119146333-T-C
• rs749944766
• NM_213649.2:c.839A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_213649.2(SFXN4):​c.839A>G​(p.Asn280Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFXN4 NM_213649.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07093227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.839A>G	p.Asn280Ser	missense_variant	Exon 13 of 14	ENST00000355697.7	NP_998814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN4	ENST00000355697.7	c.839A>G	p.Asn280Ser	missense_variant	Exon 13 of 14	1	NM_213649.2	ENSP00000347924.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.40
DANN	Benign	0.51
DEOGEN2	Benign	0.051	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.030
Sift	Benign	0.34	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.19	B;.
Vest4		0.11
MutPred		0.47		Gain of sheet (P = 0.0344);.;
MVP		0.055
MPC		0.38
ClinPred		0.064	T
GERP RS		-0.25
Varity_R		0.053
gMVP		0.24

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: rs749944766; hg19: chr10-120905845;