5-175509107-T-A

Position:

• chr5-175509107-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_022754.7(SFXN1):​c.240T>A​(p.His80Gln) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFXN1 NM_022754.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960

Genes affected

SFXN1 (HGNC:16085): (sideroflexin 1) Enables D-serine transmembrane transporter activity and L-serine transmembrane transporter activity. Involved in D-serine transport; L-serine transport; and serine import into mitochondrion. Located in mitochondrion. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

SFXN1 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN1	NM_022754.7	c.240T>A	p.His80Gln	missense_variant	3/11	ENST00000321442.10	NP_073591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN1	ENST00000321442.10	c.240T>A	p.His80Gln	missense_variant	3/11	1	NM_022754.7	ENSP00000316905.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.240T>A (p.H80Q) alteration is located in exon 3 (coding exon 2) of the SFXN1 gene. This alteration results from a T to A substitution at nucleotide position 240, causing the histidine (H) at amino acid position 80 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T;T;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Pathogenic	1.0	D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	4.1	.;H;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-7.9	D;D;.;D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D;D;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	.;D;.;D
Vest4		0.96, 0.96
MutPred		0.97		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.71
MPC		0.82
ClinPred		1.0	D
GERP RS		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-174936110;