3-13865341-A-G

Variant names:

• chr3-13865341-A-G
• rs6442414
• NM_004625.4:c.298+9606T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.9).
• 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 rank	MANE	Protein	UniProt
WNT7A	NM_004625.4	c.298+9606T>C		intron_variant	Intron 2 of 3	ENST00000285018.5	NP_004616.2
WNT7A	XM_011534091.3	c.97+9606T>C		intron_variant	Intron 3 of 4		XP_011532393.1
WNT7A	XM_047448863.1	c.97+9606T>C		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.298+9606T>C		intron_variant	Intron 2 of 3	1	NM_004625.4	ENSP00000285018.4
WNT7A	ENST00000489346.1	n.168-1440T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.726 AC: 30087 AN: 41454

American (AMR) AF: 0.669 AC: 10221 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2061 AN: 3472

East Asian (EAS) AF: 0.939 AC: 4848 AN: 5164

South Asian (SAS) AF: 0.855 AC: 4113 AN: 4812

European-Finnish (FIN) AF: 0.533 AC: 5620 AN: 10546

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39793 AN: 67986

Other (OTH) AF: 0.645 AC: 1357 AN: 2104

Alfa AF: 0.603 Hom.: 44815

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
PhyloP100		-0.34
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: rs6442414; hg19: chr3-13906838;