20-35669375-T-G

Variant names:

• chr20-35669375-T-G
• rs17092960
• NM_021100.5:c.*247A>C

Variant summary

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

The NM_021100.5(NFS1):​c.*247A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFS1 NM_021100.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 0 publications found

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]

NFS1 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 52

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000272897 (HGNC:):

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=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021100.5. 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
	NFS1	NM_021100.5	MANE Select	c.*247A>C		3_prime_UTR	Exon 13 of 13	NP_066923.3
	NFS1	NM_001198989.2		c.*247A>C		3_prime_UTR	Exon 12 of 12	NP_001185918.1	Q9Y697-3
	NFS1	NR_037570.3		n.1807A>C		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFS1	ENST00000374092.9	TSL:1 MANE Select	c.*247A>C		3_prime_UTR	Exon 13 of 13	ENSP00000363205.3	Q9Y697-1
	ENSG00000272897	ENST00000541176.2	TSL:2	n.287+3380A>C		intron	N/A	ENSP00000443983.2	H0YGN5
	NFS1	ENST00000874539.1		c.*247A>C		3_prime_UTR	Exon 13 of 13	ENSP00000544598.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 274528 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 142792

African (AFR) AF: 0.00 AC: 0 AN: 8658

American (AMR) AF: 0.00 AC: 0 AN: 11868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9072

East Asian (EAS) AF: 0.00 AC: 0 AN: 20570

South Asian (SAS) AF: 0.00 AC: 0 AN: 23074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 165374

Other (OTH) AF: 0.00 AC: 0 AN: 16452

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-1.8

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: rs17092960; hg19: chr20-34257297;