chr20-35672502-C-T

Variant names:

• chr20-35672502-C-T
• rs112782551
• NM_021100.5:c.1310+253G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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 VariationId 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.

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.1310+253G>A		intron	N/A	NP_066923.3
	NFS1	NM_001198989.2		c.1157+253G>A		intron	N/A	NP_001185918.1	Q9Y697-3
	NFS1	NR_037570.3		n.1496+253G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFS1	ENST00000374092.9	TSL:1 MANE Select	c.1310+253G>A		intron	N/A	ENSP00000363205.3	Q9Y697-1
	ENSG00000272897	ENST00000541176.2	TSL:2	n.287+253G>A		intron	N/A	ENSP00000443983.2	H0YGN5
	NFS1	ENST00000874539.1		c.1337+253G>A		intron	N/A	ENSP00000544598.1

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

African (AFR) AF: 0.0717 AC: 2979 AN: 41522

American (AMR) AF: 0.0274 AC: 419 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4818

European-Finnish (FIN) AF: 0.0578 AC: 613 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0315 AC: 2139 AN: 68012

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0413 Hom.: 19

Bravo AF: 0.0420

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism

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: rs112782551; hg19: chr20-34260424;