Genetic Variant NM_022754.7:c.*6G>A (chr5-175526740-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022754.7(SFXN1):c.*6G>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 0.165 in 1,609,326 control chromosomes in the GnomAD database, including 26,664 homozygotes. 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 0.23 ( 4970 hom., cov: 33)

Exomes 𝑓: 0.16 ( 21694 hom. )

Consequence

SFXN1
NM_022754.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN1	NM_022754.7 link	c.*6G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000321442.10	NP_073591.2	Q9H9B4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN1	ENST00000321442.10 link	c.*6G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_022754.7	ENSP00000316905.5		Q9H9B4
SFXN1	ENST00000421887.2 link	n.408G>A		non_coding_transcript_exon_variant	Exon 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34275

AN:

152144

Hom.:

4963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.194

AC:

48784

AN:

251158

Hom.:

5854

AF XY:

0.196

AC XY:

26630

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.158

AC:

230441

AN:

1457064

Hom.:

21694

Cov.:

AF XY:

0.162

AC XY:

117802

AN XY:

725230

show subpopulations

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.332

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.225

AC:

34323

AN:

152262

Hom.:

4970

Cov.:

AF XY:

0.224

AC XY:

16675

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.223

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.161

Hom.:

3014

Bravo

AF:

0.234

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.1

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over