rs759912439

Variant names:

• chr11-66422848-G-A
• rs759912439
• NM_178864.4:c.605G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-66422848-G-A
• chr11-66422848-G-T

Variant summary

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

The NM_178864.4(NPAS4):​c.605G>A​(p.Gly202Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G202V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPAS4 NM_178864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

Genes affected

NPAS4 (HGNC:18983): (neuronal PAS domain protein 4) NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008]

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=0.29583746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS4	NM_178864.4	c.605G>A	p.Gly202Asp	missense_variant	Exon 4 of 8	ENST00000311034.7	NP_849195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS4	ENST00000311034.7	c.605G>A	p.Gly202Asp	missense_variant	Exon 4 of 8	1	NM_178864.4	ENSP00000311196.2
NPAS4	ENST00000525148.1	n.605G>A		non_coding_transcript_exon_variant	Exon 4 of 7	1		ENSP00000433135.1
NPAS4	ENST00000524617.1	n.-36G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.36	.;N
REVEL	Benign	0.093
Sift	Benign	0.037	.;D
Sift4G	Benign	0.36	.;T
Polyphen		0.95	.;P
Vest4		0.78
MutPred		0.37		Loss of glycosylation at P203 (P = 0.0975);Loss of glycosylation at P203 (P = 0.0975);
MVP		0.70
MPC		0.99
ClinPred		0.88	D
GERP RS		5.3
Varity_R		0.088
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs759912439; hg19: chr11-66190319;