20-35669429-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021100.5(NFS1):c.*193A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 544,018 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (426 hom., cov: 32)
  • Exomes 𝑓: 0.061 (1066 hom.)
• Consequence: NFS1 NM_021100.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.250

Genes affected

NFS1 (HGNC:15910): (NFS1 cysteine desulfurase) Iron-sulfur clusters are required for the function of many cellular enzymes. The proteins encoded by this gene supply inorganic sulfur to these clusters by removing the sulfur from cysteine, creating alanine in the process. This gene uses alternate in-frame translation initiation sites to generate mitochondrial forms and cytoplasmic/nuclear forms. Selection of the alternative initiation sites is determined by the cytosolic pH. The encoded proteins belong to the class-V family of pyridoxal phosphate-dependent aminotransferases. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-35669429-T-C is Benign according to our data. Variant chr20-35669429-T-C is described in ClinVar as [Benign]. Clinvar id is 1289302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFS1	NM_021100.5	c.*193A>G		3_prime_UTR_variant	13/13	ENST00000374092.9
NFS1	NM_001198989.2	c.*193A>G		3_prime_UTR_variant	12/12
NFS1	NR_037570.3	n.1753A>G		non_coding_transcript_exon_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFS1	ENST00000374092.9	c.*193A>G		3_prime_UTR_variant	13/13	1	NM_021100.5	P1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10243 AN: 151694 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0489

Gnomad OTH AF: 0.0585

GnomAD4 exome AF: 0.0612 AC: 24007 AN: 392204 Hom.: 1066 Cov.: 4 AF XY: 0.0652 AC XY: 13454 AN XY: 206352

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0309

Gnomad4 ASJ exome AF: 0.0599

Gnomad4 EAS exome AF: 0.0304

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.0502

Gnomad4 OTH exome AF: 0.0603

GnomAD4 genome AF: 0.0678 AC: 10287 AN: 151814 Hom.: 426 Cov.: 32 AF XY: 0.0701 AC XY: 5200 AN XY: 74186

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0551

Gnomad4 EAS AF: 0.0501

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0488

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0523 Hom.: 225

Bravo AF: 0.0647

Asia WGS AF: 0.138 AC: 482 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.4
Dann	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2180280; hg19: chr20-34257351;