rs975021871

Variant names:

• chr20-35699326-A-C
• rs975021871
• NM_021100.5:c.-38T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-35699326-A-C
• chr20-35699326-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_021100.5(NFS1):​c.-38T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,393,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: NFS1 NM_021100.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.766
• 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]

ROMO1 (HGNC:16185): (reactive oxygen species modulator 1) The protein encoded by this gene is a mitochondrial membrane protein that is responsible for increasing the level of reactive oxygen species (ROS) in cells. The protein also has antimicrobial activity against a variety of bacteria by inducing bacterial membrane breakage. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-35699326-A-C is Benign according to our data. Variant chr20-35699326-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 512555.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-38T>G		5_prime_UTR	Exon 1 of 13	NP_066923.3
	NFS1	NM_001198989.2		c.-38T>G		5_prime_UTR	Exon 1 of 12	NP_001185918.1	Q9Y697-3
	NFS1	NR_037570.3		n.27T>G		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFS1	ENST00000374092.9	TSL:1 MANE Select	c.-38T>G		5_prime_UTR	Exon 1 of 13	ENSP00000363205.3	Q9Y697-1
	ROMO1	ENST00000374078.5	TSL:1	c.-126A>C		5_prime_UTR	Exon 1 of 3	ENSP00000363191.1	P60602-1
	NFS1	ENST00000874539.1		c.-38T>G		5_prime_UTR	Exon 1 of 13	ENSP00000544598.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000396 AC: 1 AN: 25282 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000403 AC: 50 AN: 1240914 Hom.: 0 Cov.: 27 AF XY: 0.0000366 AC XY: 22 AN XY: 600486

African (AFR) AF: 0.00 AC: 0 AN: 24456

American (AMR) AF: 0.00 AC: 0 AN: 14382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17710

East Asian (EAS) AF: 0.00 AC: 0 AN: 29332

South Asian (SAS) AF: 0.00 AC: 0 AN: 60008

European-Finnish (FIN) AF: 0.0000669 AC: 2 AN: 29892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3480

European-Non Finnish (NFE) AF: 0.0000436 AC: 44 AN: 1010262

Other (OTH) AF: 0.0000778 AC: 4 AN: 51392

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.77
PromoterAI		0.079	Neutral
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

Other links and lift over

dbSNP: rs975021871; hg19: chr20-34287248;