7-100488406-C-T

Variant names:

• chr7-100488406-C-T
• rs149154346
• NM_173564.4:c.685C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173564.4(NYAP1):​c.685C>T​(p.Arg229*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NYAP1 NM_173564.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173564.4. 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
	NYAP1	NM_173564.4	MANE Select	c.685C>T	p.Arg229*	stop_gained	Exon 4 of 7	NP_775835.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NYAP1	ENST00000300179.7	TSL:2 MANE Select	c.685C>T	p.Arg229*	stop_gained	Exon 4 of 7	ENSP00000300179.2	Q6ZVC0-1
	NYAP1	ENST00000880488.1		c.685C>T	p.Arg229*	stop_gained	Exon 4 of 7	ENSP00000550547.1
	NYAP1	ENST00000880489.1		c.685C>T	p.Arg229*	stop_gained	Exon 3 of 6	ENSP00000550548.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444684 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 718026

African (AFR) AF: 0.00 AC: 0 AN: 32716

American (AMR) AF: 0.00 AC: 0 AN: 41514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00 AC: 0 AN: 84504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104630

Other (OTH) AF: 0.00 AC: 0 AN: 59558

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	34
DANN	Uncertain	1.0
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.80	D
PhyloP100		0.0070
Vest4		0.10
GERP RS		1.7
Mutation Taster		=9/191	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs149154346; hg19: chr7-100086029; COSMIC: COSV55716957; COSMIC: COSV55716957;