20-35672502-C-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.1310+253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 152,228 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (159 hom., cov: 32)
• Consequence: NFS1 NM_021100.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.571

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=-0.93).
• BP6: Variant 20-35672502-C-T is Benign according to our data. Variant chr20-35672502-C-T is described in ClinVar as [Benign]. Clinvar id is 1269617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFS1	NM_021100.5	c.1310+253G>A		intron_variant		ENST00000374092.9
NFS1	NM_001198989.2	c.1157+253G>A		intron_variant
NFS1	NR_037570.3	n.1496+253G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFS1	ENST00000374092.9	c.1310+253G>A		intron_variant		1	NM_021100.5	P1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6536 AN: 152108 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0468

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0429 AC: 6536 AN: 152228 Hom.: 159 Cov.: 32 AF XY: 0.0431 AC XY: 3211 AN XY: 74428

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0315

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0403 Hom.: 17

Bravo AF: 0.0420

Asia WGS AF: 0.00866 AC: 30 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

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.23
Dann	Benign	0.43

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: rs112782551; hg19: chr20-34260424;