3-13855748-T-C

Variant names:

• chr3-13855748-T-C
• rs1433354
• NM_004625.4:c.299-945A>G

Variant summary

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

The NM_004625.4(WNT7A):​c.299-945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,998 control chromosomes in the GnomAD database, including 15,784 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 0.42 (15784 hom., cov: 32)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 2 publications found

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]

WNT7A Gene-Disease associations (from GenCC):

• Fuhrmann syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• phocomelia, Schinzel type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT7A	NM_004625.4	c.299-945A>G		intron_variant	Intron 2 of 3	ENST00000285018.5	NP_004616.2
WNT7A	XM_011534091.3	c.98-945A>G		intron_variant	Intron 3 of 4		XP_011532393.1
WNT7A	XM_047448863.1	c.98-945A>G		intron_variant	Intron 2 of 3		XP_047304819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT7A	ENST00000285018.5	c.299-945A>G		intron_variant	Intron 2 of 3	1	NM_004625.4	ENSP00000285018.4

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63734 AN: 151880 Hom.: 15743 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.420 AC: 63837 AN: 151998 Hom.: 15784 Cov.: 32 AF XY: 0.423 AC XY: 31389 AN XY: 74288

African (AFR) AF: 0.630 AC: 26116 AN: 41452

American (AMR) AF: 0.455 AC: 6963 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3466

East Asian (EAS) AF: 0.829 AC: 4264 AN: 5144

South Asian (SAS) AF: 0.449 AC: 2162 AN: 4812

European-Finnish (FIN) AF: 0.300 AC: 3173 AN: 10570

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19201 AN: 67954

Other (OTH) AF: 0.383 AC: 807 AN: 2108

Alfa AF: 0.334 Hom.: 18140

Bravo AF: 0.445

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.32
PhyloP100		-0.49
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: rs1433354; hg19: chr3-13897245;