14-69952282-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001034852.3(SMOC1):​c.244G>A​(p.Val82Met) variant causes a missense change. The variant allele was found at a frequency of 0.00096 in 1,614,176 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 3 hom. )

Consequence

SMOC1
NM_001034852.3 missense

Scores

6
12

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.75
Variant links:
Genes affected
SMOC1 (HGNC:20318): (SPARC related modular calcium binding 1) This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008308232).
BP6
Variant 14-69952282-G-A is Benign according to our data. Variant chr14-69952282-G-A is described in ClinVar as [Benign]. Clinvar id is 789814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-69952282-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0046 (701/152310) while in subpopulation AFR AF= 0.0155 (643/41564). AF 95% confidence interval is 0.0145. There are 4 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMOC1NM_001034852.3 linkuse as main transcriptc.244G>A p.Val82Met missense_variant 2/12 ENST00000361956.8 NP_001030024.1
SMOC1NM_022137.6 linkuse as main transcriptc.244G>A p.Val82Met missense_variant 2/12 NP_071420.1
SMOC1XM_005267995.2 linkuse as main transcriptc.244G>A p.Val82Met missense_variant 2/12 XP_005268052.1
SMOC1XM_005267996.2 linkuse as main transcriptc.244G>A p.Val82Met missense_variant 2/12 XP_005268053.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMOC1ENST00000361956.8 linkuse as main transcriptc.244G>A p.Val82Met missense_variant 2/121 NM_001034852.3 ENSP00000355110 A2Q9H4F8-2
SMOC1ENST00000381280.4 linkuse as main transcriptc.244G>A p.Val82Met missense_variant 2/121 ENSP00000370680 P4Q9H4F8-1
SMOC1ENST00000553839.1 linkuse as main transcriptn.146G>A non_coding_transcript_exon_variant 1/45
SMOC1ENST00000555917.1 linkuse as main transcriptn.549G>A non_coding_transcript_exon_variant 4/44

Frequencies

GnomAD3 genomes
AF:
0.00460
AC:
700
AN:
152192
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0155
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00123
AC:
310
AN:
251292
Hom.:
3
AF XY:
0.000957
AC XY:
130
AN XY:
135804
show subpopulations
Gnomad AFR exome
AF:
0.0156
Gnomad AMR exome
AF:
0.000925
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000580
AC:
848
AN:
1461866
Hom.:
3
Cov.:
33
AF XY:
0.000505
AC XY:
367
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0174
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.000842
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000881
Gnomad4 OTH exome
AF:
0.00131
GnomAD4 genome
AF:
0.00460
AC:
701
AN:
152310
Hom.:
4
Cov.:
33
AF XY:
0.00448
AC XY:
334
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0155
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.000917
Hom.:
1
Bravo
AF:
0.00553
ESP6500AA
AF:
0.0136
AC:
60
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00141
AC:
171
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 19, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.70
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.063
.;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
D;D
MetaRNN
Benign
0.0083
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;L
MutationTaster
Benign
0.53
N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.58
N;N
REVEL
Benign
0.092
Sift
Benign
0.058
T;T
Sift4G
Benign
0.11
T;T
Polyphen
0.61
P;D
Vest4
0.32
MVP
0.57
MPC
0.70
ClinPred
0.021
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.077
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs10150925; hg19: chr14-70418999; API