7-100486910-G-C

Variant names:

• chr7-100486910-G-C
• NM_173564.4:c.158G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173564.4(NYAP1):​c.158G>C​(p.Arg53Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NYAP1 NM_173564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77

Genes affected

NYAP1 (HGNC:22009): (neuronal tyrosine phosphorylated phosphoinositide-3-kinase adaptor 1) Predicted to be involved in neuron projection morphogenesis and phosphatidylinositol 3-kinase signaling. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYAP1	NM_173564.4	c.158G>C	p.Arg53Pro	missense_variant	Exon 3 of 7	ENST00000300179.7	NP_775835.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NYAP1	ENST00000300179.7	c.158G>C	p.Arg53Pro	missense_variant	Exon 3 of 7	2	NM_173564.4	ENSP00000300179.2
NYAP1	ENST00000454988.1	c.-14G>C		upstream_gene_variant		5		ENSP00000394424.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158G>C (p.R53P) alteration is located in exon 3 (coding exon 2) of the NYAP1 gene. This alteration results from a G to C substitution at nucleotide position 158, causing the arginine (R) at amino acid position 53 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.79	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.24
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.80
MutPred		0.23		Gain of loop (P = 0.0435);
MVP		0.10
MPC		0.89
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.54
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-100084533;