chr9-128948062-C-T

Variant names:

• chr9-128948062-C-T
• rs113796789
• NM_015354.3:c.32+311C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015354.3(NUP188):​c.32+311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 296,164 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (118 hom., cov: 31)
  • Exomes 𝑓: 0.0029 (16 hom.)
• Consequence: NUP188 NM_015354.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.842
• Publications: 2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ENSG00000251184 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 9-128948062-C-T is Benign according to our data. Variant chr9-128948062-C-T is described in ClinVar as Benign. ClinVar VariationId is 1276585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

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+311C>T		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+311C>T		intron	N/A	ENSP00000361658.2	Q5SRE5-1
	ENSG00000251184	ENST00000482796.1	TSL:2	c.39-1127C>T		intron	N/A	ENSP00000417556.2	H7C4K7
	NUP188	ENST00000550219.1	TSL:1	n.46C>T		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3145 AN: 152078 Hom.: 118 Cov.: 31

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00289 AC: 416 AN: 143968 Hom.: 16 Cov.: 0 AF XY: 0.00247 AC XY: 180 AN XY: 72936

African (AFR) AF: 0.0705 AC: 319 AN: 4522

American (AMR) AF: 0.00677 AC: 28 AN: 4134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5892

East Asian (EAS) AF: 0.00 AC: 0 AN: 13658

South Asian (SAS) AF: 0.00 AC: 0 AN: 1382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.00253 AC: 2 AN: 790

European-Non Finnish (NFE) AF: 0.000161 AC: 15 AN: 93270

Other (OTH) AF: 0.00530 AC: 52 AN: 9818

GnomAD4 genome AF: 0.0207 AC: 3152 AN: 152196 Hom.: 118 Cov.: 31 AF XY: 0.0200 AC XY: 1491 AN XY: 74418

African (AFR) AF: 0.0719 AC: 2984 AN: 41518

American (AMR) AF: 0.00765 AC: 117 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68002

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.00356 Hom.: 2

Bravo AF: 0.0244

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.61
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.84
PromoterAI		-0.057	Neutral
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: rs113796789; hg19: chr9-131710341;