rs768182696

Variant names:

• chr20-960389-C-A
• NM_001029871.4:c.673G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-960389-C-A
• chr20-960389-C-G
• chr20-960389-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029871.4(RSPO4):​c.673G>T​(p.Val225Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,386,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RSPO4 NM_001029871.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884

Genes affected

RSPO4 (HGNC:16175): (R-spondin 4) This gene encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054834098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPO4	NM_001029871.4	c.673G>T	p.Val225Leu	missense_variant	Exon 5 of 5	ENST00000217260.9	NP_001025042.2
RSPO4	NM_001040007.3	c.487G>T	p.Val163Leu	missense_variant	Exon 4 of 4		NP_001035096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPO4	ENST00000217260.9	c.673G>T	p.Val225Leu	missense_variant	Exon 5 of 5	1	NM_001029871.4	ENSP00000217260.4
RSPO4	ENST00000400634.2	c.487G>T	p.Val163Leu	missense_variant	Exon 4 of 4	1		ENSP00000383475.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1386138 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 684160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.064
DANN	Benign	0.51
DEOGEN2	Benign	0.050	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.54	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.10
Sift	Benign	0.36	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.15	B;B
Vest4		0.063
MutPred		0.19		Loss of MoRF binding (P = 0.0994);.;
MVP		0.32
MPC		0.053
ClinPred		0.11	T
GERP RS		-0.038
Varity_R		0.031
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-941032;