chr9-128958855-C-T

Variant names:

• chr9-128958855-C-T
• rs1480414493
• NM_015354.3:c.426C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_015354.3(NUP188):​c.426C>T​(p.His142His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,450,290 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: NUP188 NM_015354.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.235
• Publications: 0 publications found

Genes affected

NUP188 (HGNC:17859): (nucleoporin 188) The nuclear pore complex (NPC) is found on the nuclear envelope and forms a gateway that regulates the flow of proteins and RNAs between the cytoplasm and nucleoplasm. The NPC is comprised of approximately 30 distinct proteins collectively known as nucleoporins. Nucleoporins are pore-complex-specific glycoproteins which often have cytoplasmically oriented O-linked N-acetylglucosamine residues and numerous repeats of the pentapeptide sequence XFXFG. However, the nucleoporin protein encoded by this gene does not contain the typical FG repeat sequences found in most vertebrate nucleoporins. This nucleoporin is thought to form part of the scaffold for the central channel of the nuclear pore. [provided by RefSeq, Jan 2013]

NUP188 Gene-Disease associations (from GenCC):

• sandestig-stefanova syndrome

  Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 9-128958855-C-T is Benign according to our data. Variant chr9-128958855-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 797740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.235 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015354.3. 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
	NUP188	NM_015354.3	MANE Select	c.426C>T	p.His142His	synonymous	Exon 7 of 44	NP_056169.1	Q5SRE5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP188	ENST00000372577.2	TSL:1 MANE Select	c.426C>T	p.His142His	synonymous	Exon 7 of 44	ENSP00000361658.2	Q5SRE5-1
	NUP188	ENST00000935260.1		c.633C>T	p.His211His	synonymous	Exon 8 of 45	ENSP00000605319.1
	NUP188	ENST00000935265.1		c.426C>T	p.His142His	synonymous	Exon 7 of 45	ENSP00000605324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000483 AC: 7 AN: 1450290 Hom.: 0 Cov.: 29 AF XY: 0.00000555 AC XY: 4 AN XY: 721278

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 84262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5510

European-Non Finnish (NFE) AF: 0.00000634 AC: 7 AN: 1104826

Other (OTH) AF: 0.00 AC: 0 AN: 59780

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	-0.35
CADD	Benign	7.6
DANN	Benign	0.76
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1480414493; hg19: chr9-131721134;