7-16462820-C-G

Position:

• chr7-16462820-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015464.3(SOSTDC1):​c.349G>C​(p.Gly117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOSTDC1 NM_015464.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

Genes affected

SOSTDC1 (HGNC:21748): (sclerostin domain containing 1) This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death. [provided by RefSeq, Jul 2008]

CRPPA (HGNC:37276): (CDP-L-ribitol pyrophosphorylase A) This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

LOC105375168 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41474813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOSTDC1	NM_015464.3	c.349G>C	p.Gly117Arg	missense_variant	2/2	ENST00000307068.5	NP_056279.1
LOC105375168	XR_007060220.1	n.736+1504C>G		intron_variant
LOC105375168	XR_007060223.1	n.581-7800C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOSTDC1	ENST00000307068.5	c.349G>C	p.Gly117Arg	missense_variant	2/2	1	NM_015464.3	ENSP00000304930.4
SOSTDC1	ENST00000396652.1	c.421G>C	p.Gly141Arg	missense_variant	5/5	2		ENSP00000379889.1
CRPPA	ENST00000675257.1	c.-47+33560G>C		intron_variant				ENSP00000501664.1
CRPPA	ENST00000674759.1	c.-47+33560G>C		intron_variant				ENSP00000502749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 23, 2024

The c.349G>C (p.G117R) alteration is located in exon 2 (coding exon 2) of the SOSTDC1 gene. This alteration results from a G to C substitution at nucleotide position 349, causing the glycine (G) at amino acid position 117 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.71	D;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.45	P;.
Vest4		0.27
MutPred		0.75		Gain of MoRF binding (P = 0.0155);.;
MVP		0.85
MPC		0.87
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-16502445;