rs145072749

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-128947907-A-C
• chr9-128947907-A-G

Variant summary

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

The NM_015354.3(NUP188):​c.32+156A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000708 in 424,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: NUP188 NM_015354.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000708 AC: 3 AN: 424012 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 211442

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9934

American (AMR) AF: 0.00 AC: 0 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: 0.00000963 AC: 3 AN: 311572

Other (OTH) AF: 0.00 AC: 0 AN: 22384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.67
PhyloP100		1.5
PromoterAI		0.082	Neutral

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;