chr9-128947907-A-G

Variant names:

• chr9-128947907-A-G
• rs145072749
• NM_015354.3:c.32+156A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_015354.3(NUP188):​c.32+156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 574,882 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (20 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (11 hom.)
• Consequence: NUP188 NM_015354.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.47
• 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

ENSG00000251184 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 9-128947907-A-G is Benign according to our data. Variant chr9-128947907-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 673511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00953 (1438/150870) while in subpopulation AFR AF = 0.0331 (1361/41106). AF 95% confidence interval is 0.0316. There are 20 homozygotes in GnomAd4. There are 672 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR,Unknown gene

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.32+156A>G		intron	N/A	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.32+156A>G		intron	N/A	ENSP00000361658.2	Q5SRE5-1
	ENSG00000251184	ENST00000482796.1	TSL:2	c.39-1282A>G		intron	N/A	ENSP00000417556.2	H7C4K7
	NUP188	ENST00000935260.1		c.32+156A>G		intron	N/A	ENSP00000605319.1

Frequencies

GnomAD3 genomes AF: 0.00952 AC: 1435 AN: 150756 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00362

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00483

GnomAD4 exome AF: 0.00118 AC: 499 AN: 424012 Hom.: 11 Cov.: 6 AF XY: 0.00106 AC XY: 224 AN XY: 211442

African (AFR) AF: 0.0349 AC: 347 AN: 9932

American (AMR) AF: 0.00372 AC: 36 AN: 9680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10412

East Asian (EAS) AF: 0.00 AC: 0 AN: 24212

South Asian (SAS) AF: 0.00 AC: 0 AN: 11872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2070

European-Non Finnish (NFE) AF: 0.000154 AC: 48 AN: 311574

Other (OTH) AF: 0.00304 AC: 68 AN: 22384

GnomAD4 genome AF: 0.00953 AC: 1438 AN: 150870 Hom.: 20 Cov.: 31 AF XY: 0.00912 AC XY: 672 AN XY: 73686

African (AFR) AF: 0.0331 AC: 1361 AN: 41106

American (AMR) AF: 0.00362 AC: 55 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5010

South Asian (SAS) AF: 0.000421 AC: 2 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10448

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67600

Other (OTH) AF: 0.00478 AC: 10 AN: 2092

Alfa AF: 0.00687 Hom.: 1

Bravo AF: 0.0109

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.67
PhyloP100		1.5
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs145072749; hg19: chr9-131710186;