rs199557439

Variant names:

• chr1-5909173-C-A
• NM_015102.5:c.1482G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-5909173-C-A
• chr1-5909173-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015102.5(NPHP4):​c.1482G>T​(p.Gln494His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q494Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPHP4 NM_015102.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

Genes affected

NPHP4 (HGNC:19104): (nephrocystin 4) This gene encodes a protein involved in renal tubular development and function. This protein interacts with nephrocystin, and belongs to a multifunctional complex that is localized to actin- and microtubule-based structures. Mutations in this gene are associated with nephronophthisis type 4, a renal disease, and with Senior-Loken syndrome type 4, a combination of nephronophthisis and retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29112822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHP4	NM_015102.5	c.1482G>T	p.Gln494His	missense_variant	Exon 12 of 30	ENST00000378156.9	NP_055917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPHP4	ENST00000378156.9	c.1482G>T	p.Gln494His	missense_variant	Exon 12 of 30	1	NM_015102.5	ENSP00000367398.4
NPHP4	ENST00000489180.6	n.1482G>T		non_coding_transcript_exon_variant	Exon 12 of 33	2		ENSP00000423747.1
NPHP4	ENST00000378169.7	n.*516-3393G>T		intron_variant	Intron 10 of 26	1		ENSP00000367411.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450306 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.28
Sift	Benign	0.046	D;.
Sift4G	Benign	0.52	T;T
Polyphen		0.063	B;.
Vest4		0.43
MutPred		0.045		Gain of glycosylation at S496 (P = 0.1734);Gain of glycosylation at S496 (P = 0.1734);
MVP		0.87
MPC		0.080
ClinPred		0.094	T
GERP RS		1.6
Varity_R		0.047
gMVP		0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-5969233; COSMIC: COSV100976956; COSMIC: COSV100976956;