rs3762719

Variant names:

• chr3-13854643-A-G
• rs3762719
• NM_004625.4:c.459T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-13854643-A-G
• chr3-13854643-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004625.4(WNT7A):​c.459T>C​(p.Ser153Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,613,998 control chromosomes in the GnomAD database, including 35,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3281 hom., cov: 33)
  • Exomes 𝑓: 0.20 (32519 hom.)
• Consequence: WNT7A NM_004625.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.464
• Publications: 17 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, Orphanet, Labcorp Genetics (formerly Invitae)
• phocomelia, Schinzel type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-13854643-A-G is Benign according to our data. Variant chr3-13854643-A-G is described in ClinVar as Benign. ClinVar VariationId is 1291668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.464 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7A	NM_004625.4	MANE Select	c.459T>C	p.Ser153Ser	synonymous	Exon 3 of 4	NP_004616.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7A	ENST00000285018.5	TSL:1 MANE Select	c.459T>C	p.Ser153Ser	synonymous	Exon 3 of 4	ENSP00000285018.4	O00755

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29521 AN: 152052 Hom.: 3273 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.216 AC: 54274 AN: 251326 AF XY: 0.211

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.201 AC: 293815 AN: 1461826 Hom.: 32519 Cov.: 39 AF XY: 0.200 AC XY: 145307 AN XY: 727218

African (AFR) AF: 0.164 AC: 5478 AN: 33480

American (AMR) AF: 0.220 AC: 9849 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3166 AN: 26136

East Asian (EAS) AF: 0.549 AC: 21776 AN: 39700

South Asian (SAS) AF: 0.185 AC: 15996 AN: 86258

European-Finnish (FIN) AF: 0.203 AC: 10838 AN: 53356

Middle Eastern (MID) AF: 0.150 AC: 866 AN: 5768

European-Non Finnish (NFE) AF: 0.192 AC: 213849 AN: 1112008

Other (OTH) AF: 0.199 AC: 11997 AN: 60396

GnomAD4 genome AF: 0.194 AC: 29557 AN: 152172 Hom.: 3281 Cov.: 33 AF XY: 0.196 AC XY: 14606 AN XY: 74394

African (AFR) AF: 0.171 AC: 7096 AN: 41516

American (AMR) AF: 0.192 AC: 2932 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3468

East Asian (EAS) AF: 0.560 AC: 2880 AN: 5144

South Asian (SAS) AF: 0.197 AC: 948 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2194 AN: 10598

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12598 AN: 68008

Other (OTH) AF: 0.162 AC: 343 AN: 2112

Alfa AF: 0.177 Hom.: 1090

Bravo AF: 0.194

Asia WGS AF: 0.346 AC: 1202 AN: 3478

EpiCase AF: 0.178

EpiControl AF: 0.177

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		-0.46
Mutation Taster		=98/2	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: rs3762719; hg19: chr3-13896140; COSMIC: COSV53197438;