rs113241875

Variant names:

• chr9-128947738-G-A
• rs113241875
• NM_015354.3:c.19G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-128947738-G-A
• chr9-128947738-G-C
• chr9-128947738-G-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.19G>A​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,474,308 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (115 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (101 hom.)
• Consequence: NUP188 NM_015354.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.42
• Publications: 6 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]

ENSG00000251184 (HGNC:):

DOLK (HGNC:23406): (dolichol kinase) The protein encoded by this gene catalyzes the CTP-mediated phosphorylation of dolichol, and is involved in the synthesis of Dol-P-Man, which is an essential glycosyl carrier lipid for C- and O-mannosylation, N- and O-linked glycosylation of proteins, and for the biosynthesis of glycosyl phosphatidylinositol anchors in endoplasmic reticulum. Mutations in this gene are associated with dolichol kinase deficiency.[provided by RefSeq, Apr 2010]

DOLK Gene-Disease associations (from GenCC):

• DK1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.002246201).
• BP6: Variant 9-128947738-G-A is Benign according to our data. Variant chr9-128947738-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 369621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 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.19G>A	p.Gly7Arg	missense	Exon 1 of 44	NP_056169.1	Q5SRE5-1
	DOLK	NM_014908.4	MANE Select	c.-435C>T		upstream_gene	N/A	NP_055723.1	Q9UPQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP188	ENST00000372577.2	TSL:1 MANE Select	c.19G>A	p.Gly7Arg	missense	Exon 1 of 44	ENSP00000361658.2	Q5SRE5-1
	ENSG00000251184	ENST00000482796.1	TSL:2	c.39-1451G>A		intron	N/A	ENSP00000417556.2	H7C4K7
	NUP188	ENST00000935260.1		c.19G>A	p.Gly7Arg	missense	Exon 1 of 45	ENSP00000605319.1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3131 AN: 152072 Hom.: 115 Cov.: 31

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

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

GnomAD2 exomes AF: 0.00461 AC: 417 AN: 90426 AF XY: 0.00348

Gnomad AFR exome AF: 0.0785

Gnomad AMR exome AF: 0.00299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00206 AC: 2727 AN: 1322118 Hom.: 101 Cov.: 31 AF XY: 0.00179 AC XY: 1161 AN XY: 648408

African (AFR) AF: 0.0801 AC: 2237 AN: 27926

American (AMR) AF: 0.00378 AC: 98 AN: 25934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21928

East Asian (EAS) AF: 0.00 AC: 0 AN: 32804

South Asian (SAS) AF: 0.000167 AC: 12 AN: 71736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34442

Middle Eastern (MID) AF: 0.00372 AC: 19 AN: 5104

European-Non Finnish (NFE) AF: 0.000103 AC: 108 AN: 1047356

Other (OTH) AF: 0.00461 AC: 253 AN: 54888

GnomAD4 genome AF: 0.0206 AC: 3138 AN: 152190 Hom.: 115 Cov.: 31 AF XY: 0.0200 AC XY: 1487 AN XY: 74416

African (AFR) AF: 0.0715 AC: 2969 AN: 41546

American (AMR) AF: 0.00772 AC: 118 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67998

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00607 Hom.: 70

Bravo AF: 0.0243

ESP6500AA AF: 0.0517 AC: 178

ESP6500EA AF: 0.000305 AC: 2

ExAC AF: 0.00334 AC: 174

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.4
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.092
Sift	Benign	0.077	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.29
MutPred		0.39		Gain of MoRF binding (P = 1e-04)
MVP		0.068
MPC		0.22
ClinPred		0.043	T
GERP RS		3.6
PromoterAI		0.095	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2
Varity_R		0.085
gMVP		0.25
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs113241875; hg19: chr9-131710017;