20-35669362-G-T

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.*260C>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 0.0999 in 382,406 control chromosomes in the GnomAD database, including 2,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (789 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1284 hom.)
• Consequence: NFS1 NM_021100.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425

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=-0.9).
• BP6: Variant 20-35669362-G-T is Benign according to our data. Variant chr20-35669362-G-T is described in ClinVar as [Benign]. Clinvar id is 1236960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFS1	NM_021100.5	c.*260C>A		3_prime_UTR_variant	13/13	ENST00000374092.9
NFS1	NM_001198989.2	c.*260C>A		3_prime_UTR_variant	12/12
NFS1	NR_037570.3	n.1820C>A		non_coding_transcript_exon_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFS1	ENST00000374092.9	c.*260C>A		3_prime_UTR_variant	13/13	1	NM_021100.5	P1

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15170 AN: 152116 Hom.: 788 Cov.: 32

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0787

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.100 AC: 23024 AN: 230172 Hom.: 1284 Cov.: 0 AF XY: 0.104 AC XY: 12434 AN XY: 119556

Gnomad4 AFR exome AF: 0.0862

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0728

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0731

Gnomad4 NFE exome AF: 0.0986

Gnomad4 OTH exome AF: 0.0977

GnomAD4 genome AF: 0.0997 AC: 15171 AN: 152234 Hom.: 789 Cov.: 32 AF XY: 0.0988 AC XY: 7355 AN XY: 74452

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0787

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.111

Alfa AF: 0.102 Hom.: 228

Bravo AF: 0.0996

Asia WGS AF: 0.145 AC: 502 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 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.45
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs7267759; hg19: chr20-34257284;