chr7-100488290-A-C

Variant names:

• chr7-100488290-A-C
• rs145361652
• NM_173564.4:c.569A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173564.4(NYAP1):​c.569A>C​(p.Asn190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N190S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NYAP1 NM_173564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04078874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYAP1	NM_173564.4	c.569A>C	p.Asn190Thr	missense_variant	Exon 4 of 7	ENST00000300179.7	NP_775835.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NYAP1	ENST00000300179.7	c.569A>C	p.Asn190Thr	missense_variant	Exon 4 of 7	2	NM_173564.4	ENSP00000300179.2
NYAP1	ENST00000454988.1	c.398A>C	p.Asn133Thr	missense_variant	Exon 2 of 5	5		ENSP00000394424.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000643 AC: 94 AN: 1460878 Hom.: 0 Cov.: 34 AF XY: 0.0000633 AC XY: 46 AN XY: 726790

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00127

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152034 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74256

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.000577 AC: 70

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.79
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.055
Sift	Benign	0.29	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.071	B;.
Vest4		0.35
MVP		0.043
MPC		0.21
ClinPred		0.0075	T
GERP RS		0.86
Varity_R		0.044
gMVP		0.13

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: rs145361652; hg19: chr7-100085913;