NM_017547.4:c.-15G>T

Variant names:

• chr11-126269192-G-T
• rs201288313
• NM_017547.4:c.-15G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017547.4(FOXRED1):​c.-15G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FOXRED1 NM_017547.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 1 publications found

Genes affected

FOXRED1 (HGNC:26927): (FAD dependent oxidoreductase domain containing 1) This gene encodes a protein that contains a FAD-dependent oxidoreductase domain. The encoded protein is localized to the mitochondria and may function as a chaperone protein required for the function of mitochondrial complex I. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

SRPRA Gene-Disease associations (from GenCC):

• Shwachman-Diamond syndrome

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017547.4. 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
	FOXRED1	NM_017547.4	MANE Select	c.-15G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_060017.1	Q96CU9-1
	FOXRED1	NM_017547.4	MANE Select	c.-15G>T		5_prime_UTR	Exon 1 of 11	NP_060017.1	Q96CU9-1
	FOXRED1	NM_001425160.1		c.-15G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001412089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXRED1	ENST00000263578.10	TSL:1 MANE Select	c.-15G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000263578.5	Q96CU9-1
	FOXRED1	ENST00000263578.10	TSL:1 MANE Select	c.-15G>T		5_prime_UTR	Exon 1 of 11	ENSP00000263578.5	Q96CU9-1
	FOXRED1	ENST00000853296.1		c.-15G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000523355.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249682 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1448722 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 721576

African (AFR) AF: 0.00 AC: 0 AN: 33272

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5064

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100864

Other (OTH) AF: 0.0000334 AC: 2 AN: 59896

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.68
DANN	Benign	0.55
PhyloP100		-2.3
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs201288313; hg19: chr11-126139087;