7-16462576-CT-C

Position:

• chr7-16462576-CT-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_015464.3(SOSTDC1):​c.592delA​(p.Ser198fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,614,176 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (21 hom.)
• Consequence: SOSTDC1 NM_015464.3 frameshift
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 7-16462576-CT-C is Benign according to our data. Variant chr7-16462576-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 791269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 596 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOSTDC1	NM_015464.3	c.592delA	p.Ser198fs	frameshift_variant	2/2	ENST00000307068.5	NP_056279.1
LOC105375168	XR_007060220.1	n.736+1261delT		intron_variant
LOC105375168	XR_007060223.1	n.581-8043delT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOSTDC1	ENST00000307068.5	c.592delA	p.Ser198fs	frameshift_variant	2/2	1	NM_015464.3	ENSP00000304930.4
SOSTDC1	ENST00000396652.1	c.664delA	p.Ser222fs	frameshift_variant	5/5	2		ENSP00000379889.1
CRPPA	ENST00000675257.1	c.-47+33803delA		intron_variant				ENSP00000501664.1
CRPPA	ENST00000674759.1	c.-47+33803delA		intron_variant				ENSP00000502749.1

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 596 AN: 152188 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00392

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00394 AC: 990 AN: 251228 Hom.: 8 AF XY: 0.00395 AC XY: 536 AN XY: 135760

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00427

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.0201

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00329 AC: 4804 AN: 1461870 Hom.: 21 Cov.: 31 AF XY: 0.00332 AC XY: 2417 AN XY: 727232

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.00383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00105

Gnomad4 FIN exome AF: 0.0180

Gnomad4 NFE exome AF: 0.00299

Gnomad4 OTH exome AF: 0.00320

GnomAD4 genome AF: 0.00391 AC: 596 AN: 152306 Hom.: 5 Cov.: 32 AF XY: 0.00465 AC XY: 346 AN XY: 74472

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.00393

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00113 Hom.: 1

Bravo AF: 0.00249

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	SOSTDC1: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

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: rs554609300; hg19: chr7-16502201;