NM_012479.4:c.87+2487C>T

Variant names:

• chr7-76356235-G-A
• rs17149177
• NM_012479.4:c.87+2487C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012479.4(YWHAG):​c.87+2487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,120 control chromosomes in the GnomAD database, including 2,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2840 hom., cov: 33)
• Consequence: YWHAG NM_012479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 8 publications found

Genes affected

YWHAG (HGNC:12852): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma) This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the rat ortholog. It is induced by growth factors in human vascular smooth muscle cells, and is also highly expressed in skeletal and heart muscles, suggesting an important role for this protein in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. [provided by RefSeq, Jul 2008]

YWHAG Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 56

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAG	NM_012479.4	c.87+2487C>T		intron_variant	Intron 1 of 1	ENST00000307630.5	NP_036611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAG	ENST00000307630.5	c.87+2487C>T		intron_variant	Intron 1 of 1	1	NM_012479.4	ENSP00000306330.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26596 AN: 152004 Hom.: 2838 Cov.: 33

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26598 AN: 152120 Hom.: 2840 Cov.: 33 AF XY: 0.177 AC XY: 13141 AN XY: 74346

African (AFR) AF: 0.0646 AC: 2681 AN: 41518

American (AMR) AF: 0.239 AC: 3645 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1716 AN: 5178

South Asian (SAS) AF: 0.255 AC: 1231 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1932 AN: 10560

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13939 AN: 67992

Other (OTH) AF: 0.181 AC: 380 AN: 2102

Alfa AF: 0.201 Hom.: 4444

Bravo AF: 0.174

Asia WGS AF: 0.280 AC: 968 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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: rs17149177; hg19: chr7-75985552;