7-121339025-T-C

Position:

• chr7-121339025-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_057168.2(WNT16):​c.778T>C​(p.Ser260Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,614,040 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (6 hom.)
• Consequence: WNT16 NM_057168.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.17

Genes affected

WNT16 (HGNC:16267): (Wnt family member 16) The WNT gene family consists of structurally related genes which 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 a member of the WNT gene family. It contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00790751).
• BP6: Variant 7-121339025-T-C is Benign according to our data. Variant chr7-121339025-T-C is described in ClinVar as [Benign]. Clinvar id is 773396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00558 (849/152208) while in subpopulation AFR AF= 0.0186 (774/41526). AF 95% confidence interval is 0.0176. There are 9 homozygotes in gnomad4. There are 392 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT16	NM_057168.2	c.778T>C	p.Ser260Pro	missense_variant	4/4	ENST00000222462.3	NP_476509.1
WNT16	NM_016087.2	c.748T>C	p.Ser250Pro	missense_variant	4/4		NP_057171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT16	ENST00000222462.3	c.778T>C	p.Ser260Pro	missense_variant	4/4	1	NM_057168.2	ENSP00000222462	P1
WNT16	ENST00000361301.6	c.748T>C	p.Ser250Pro	missense_variant	4/4	1		ENSP00000355065

Frequencies

GnomAD3 genomes AF: 0.00558 AC: 849 AN: 152090 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00159 AC: 399 AN: 251058 Hom.: 1 AF XY: 0.00122 AC XY: 166 AN XY: 135700

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000770 AC: 1126 AN: 1461832 Hom.: 6 Cov.: 30 AF XY: 0.000683 AC XY: 497 AN XY: 727212

Gnomad4 AFR exome AF: 0.0201

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00241

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00558 AC: 849 AN: 152208 Hom.: 9 Cov.: 32 AF XY: 0.00527 AC XY: 392 AN XY: 74416

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00109 Hom.: 3

Bravo AF: 0.00651

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0191 AC: 84

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00185 AC: 224

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	.;D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.78	T;T
MetaRNN	Benign	0.0079	T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.3	.;L
MutationTaster	Benign	0.73	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.25	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.91	P;D
Vest4		0.60
MVP		0.95
MPC		0.61
ClinPred		0.029	T
GERP RS		5.5
Varity_R		0.75
gMVP		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: rs116444834; hg19: chr7-120979079;