chr10-101037108-AG-A

Variant names:

• chr10-101037108-AG-A
• rs563028036
• NM_030971.6:c.628delG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_030971.6(SFXN3):​c.628delG​(p.Ala210GlnfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,613,956 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (16 hom.)
• Consequence: SFXN3 NM_030971.6 frameshift
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.90
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

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.628delG	p.Ala210GlnfsTer9	frameshift	Exon 8 of 12	NP_112233.3
	SFXN3	NM_001388027.1		c.652delG	p.Ala218GlnfsTer9	frameshift	Exon 8 of 12	NP_001374956.1	B4DRS6
	SFXN3	NM_001388028.1		c.652delG	p.Ala218GlnfsTer9	frameshift	Exon 8 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.628delG	p.Ala210GlnfsTer9	frameshift	Exon 8 of 12	ENSP00000377103.1	Q9BWM7
	SFXN3	ENST00000698791.1		c.640delG	p.Ala214GlnfsTer9	frameshift	Exon 7 of 11	ENSP00000513933.1	A0A8V8TP06
	SFXN3	ENST00000896239.1		c.628delG	p.Ala210GlnfsTer9	frameshift	Exon 8 of 12	ENSP00000566298.1

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 332 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00199 AC: 499 AN: 250974 AF XY: 0.00202

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00329

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00394 AC: 5761 AN: 1461770 Hom.: 16 Cov.: 35 AF XY: 0.00383 AC XY: 2788 AN XY: 727178

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.00333 AC: 149 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53310

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00482 AC: 5364 AN: 1112008

Other (OTH) AF: 0.00364 AC: 220 AN: 60394

GnomAD4 genome AF: 0.00219 AC: 333 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74402

African (AFR) AF: 0.000674 AC: 28 AN: 41518

American (AMR) AF: 0.00445 AC: 68 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00337 AC: 229 AN: 67992

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.000528 Hom.: 0

Bravo AF: 0.00262

EpiCase AF: 0.00322

EpiControl AF: 0.00403

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Neurodevelopmental disorder (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=136/64	disease causing (fs/PTC)

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

dbSNP: rs563028036; hg19: chr10-102796865; COSMIC: COSV99827471; COSMIC: COSV99827471;