rs750059875

Variant names:

• chr2-127503469-C-A
• rs750059875
• NM_017969.3:c.1327G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-127503469-C-A
• chr2-127503469-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017969.3(IWS1):​c.1327G>T​(p.Glu443*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IWS1 NM_017969.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14
• Publications: 0 publications found

Genes affected

IWS1 (HGNC:25467): (interacts with SUPT6H, CTD assembly factor 1) Involved in regulation of histone modification; regulation of mRNA export from nucleus; and regulation of mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000231731 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017969.3. 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
	IWS1	NM_017969.3	MANE Select	c.1327G>T	p.Glu443*	stop_gained	Exon 4 of 14	NP_060439.2	Q96ST2-1
	IWS1	NM_001410923.1		c.1327G>T	p.Glu443*	stop_gained	Exon 4 of 15	NP_001397852.1	A0A1B0GW95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IWS1	ENST00000295321.9	TSL:1 MANE Select	c.1327G>T	p.Glu443*	stop_gained	Exon 4 of 14	ENSP00000295321.4	Q96ST2-1
	IWS1	ENST00000637187.2	TSL:5	c.1327G>T	p.Glu443*	stop_gained	Exon 4 of 15	ENSP00000490836.2	A0A1B0GW95
	IWS1	ENST00000866713.1		c.1324G>T	p.Glu442*	stop_gained	Exon 4 of 14	ENSP00000536772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251008 AF XY: 0.00000737

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461282 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726966

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111716

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.1
Vest4		0.44
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=3/197	disease causing (fs/PTC)

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: rs750059875; hg19: chr2-128261045;