NM_030971.6:c.781T>C

Variant names:

• chr10-101038652-T-C
• NM_030971.6:c.781T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030971.6(SFXN3):​c.781T>C​(p.Trp261Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFXN3 NM_030971.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

Genes affected

SFXN3 (HGNC:16087): (sideroflexin 3) Enables serine transmembrane transporter activity. Involved in serine import into mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4101714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030971.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN3	NM_030971.6	MANE Select	c.781T>C	p.Trp261Arg	missense	Exon 10 of 12	NP_112233.3
	SFXN3	NM_001388027.1		c.805T>C	p.Trp269Arg	missense	Exon 10 of 12	NP_001374956.1	B4DRS6
	SFXN3	NM_001388028.1		c.805T>C	p.Trp269Arg	missense	Exon 10 of 12	NP_001374957.1	B4DRS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN3	ENST00000393459.6	TSL:5 MANE Select	c.781T>C	p.Trp261Arg	missense	Exon 10 of 12	ENSP00000377103.1	Q9BWM7
	SFXN3	ENST00000698791.1		c.793T>C	p.Trp265Arg	missense	Exon 9 of 11	ENSP00000513933.1	A0A8V8TP06
	SFXN3	ENST00000896239.1		c.781T>C	p.Trp261Arg	missense	Exon 10 of 12	ENSP00000566298.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Benign	0.92
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.18
Sift	Benign	0.27	T
Sift4G	Benign	0.45	T
Vest4		0.54
MutPred		0.52		Gain of methylation at W265 (P = 0.0071)
MVP		0.27
MPC		0.37
ClinPred		0.68	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.63
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr10-102798409;