3-13841863-T-C

Variant names:

• chr3-13841863-T-C
• rs9863149
• NM_004625.4:c.570+12669A>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.570+12669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,812 control chromosomes in the GnomAD database, including 9,407 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 0.34 (9407 hom., cov: 32)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT7A	NM_004625.4	c.570+12669A>G		intron_variant	Intron 3 of 3	ENST00000285018.5	NP_004616.2
WNT7A	XM_011534091.3	c.369+12669A>G		intron_variant	Intron 4 of 4		XP_011532393.1
WNT7A	XM_047448863.1	c.369+12669A>G		intron_variant	Intron 3 of 3		XP_047304819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT7A	ENST00000285018.5	c.570+12669A>G		intron_variant	Intron 3 of 3	1	NM_004625.4	ENSP00000285018.4

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52319 AN: 151694 Hom.: 9395 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.345 AC: 52367 AN: 151812 Hom.: 9407 Cov.: 32 AF XY: 0.344 AC XY: 25525 AN XY: 74204

African (AFR) AF: 0.447 AC: 18524 AN: 41396

American (AMR) AF: 0.306 AC: 4676 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1321 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1443 AN: 5162

South Asian (SAS) AF: 0.450 AC: 2156 AN: 4788

European-Finnish (FIN) AF: 0.242 AC: 2546 AN: 10530

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20483 AN: 67886

Other (OTH) AF: 0.365 AC: 771 AN: 2110

Alfa AF: 0.318 Hom.: 32799

Bravo AF: 0.350

Asia WGS AF: 0.373 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		-0.56
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: rs9863149; hg19: chr3-13883360;