3-13865341-A-G

Position:

• chr3-13865341-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004625.4(WNT7A):​c.298+9606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,028 control chromosomes in the GnomAD database, including 32,906 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 0.65 (32906 hom., cov: 31)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

Genes affected

WNT7A (HGNC:12786): (Wnt family member 7A) This gene is a member of the WNT gene family, which consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is involved in the development of the anterior-posterior axis in the female reproductive tract, and also plays a critical role in uterine smooth muscle pattering and maintenance of adult uterine function. Mutations in this gene are associated with Fuhrmann and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndromes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT7A	NM_004625.4	c.298+9606T>C		intron_variant		ENST00000285018.5	NP_004616.2
WNT7A	XM_011534091.3	c.97+9606T>C		intron_variant			XP_011532393.1
WNT7A	XM_047448863.1	c.97+9606T>C		intron_variant			XP_047304819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT7A	ENST00000285018.5	c.298+9606T>C		intron_variant		1	NM_004625.4	ENSP00000285018	P1
WNT7A	ENST00000489346.1	n.168-1440T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98751 AN: 151910 Hom.: 32868 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.650 AC: 98852 AN: 152028 Hom.: 32906 Cov.: 31 AF XY: 0.655 AC XY: 48682 AN XY: 74308

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.645

Alfa AF: 0.598 Hom.: 34284

Bravo AF: 0.664

Asia WGS AF: 0.878 AC: 3049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.64

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: rs6442414; hg19: chr3-13906838;