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GeneBe

7-16462821-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015464.3(SOSTDC1):c.348A>G(p.Gly116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,100 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00079 ( 6 hom. )

Consequence

SOSTDC1
NM_015464.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.131
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-16462821-T-C is Benign according to our data. Variant chr7-16462821-T-C is described in ClinVar as [Benign]. Clinvar id is 723269.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.131 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 650 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOSTDC1NM_015464.3 linkuse as main transcriptc.348A>G p.Gly116= synonymous_variant 2/2 ENST00000307068.5
LOC105375168XR_007060223.1 linkuse as main transcriptn.581-7799T>C intron_variant, non_coding_transcript_variant
LOC105375168XR_007060220.1 linkuse as main transcriptn.736+1505T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOSTDC1ENST00000307068.5 linkuse as main transcriptc.348A>G p.Gly116= synonymous_variant 2/21 NM_015464.3 P1Q6X4U4-1
SOSTDC1ENST00000396652.1 linkuse as main transcriptc.420A>G p.Gly140= synonymous_variant 5/52 Q6X4U4-2
CRPPAENST00000674759.1 linkuse as main transcriptc.-47+33559A>G intron_variant
CRPPAENST00000675257.1 linkuse as main transcriptc.-47+33559A>G intron_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00427
AC:
650
AN:
152092
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0134
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00360
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00172
AC:
431
AN:
251280
Hom.:
4
AF XY:
0.00144
AC XY:
196
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.0137
Gnomad AMR exome
AF:
0.00324
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000467
Gnomad OTH exome
AF:
0.00456
GnomAD4 exome
AF:
0.000793
AC:
1160
AN:
1461890
Hom.:
6
Cov.:
31
AF XY:
0.000792
AC XY:
576
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0138
Gnomad4 AMR exome
AF:
0.00340
Gnomad4 ASJ exome
AF:
0.00126
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000341
Gnomad4 OTH exome
AF:
0.00190
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00428
AC:
651
AN:
152210
Hom.:
5
Cov.:
32
AF XY:
0.00449
AC XY:
334
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.0133
Gnomad4 AMR
AF:
0.00360
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00238
Hom.:
1
Bravo
AF:
0.00539
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.000711

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
6.3
Dann
Benign
0.70

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34300902; hg19: chr7-16502446; API