Genetic Variant SMOC1:n.404+15059T>A (chr14-69879273-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000555917.1(SMOC1):n.404+15059T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 167,176 control chromosomes in the GnomAD database, including 2,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 2886 hom., cov: 32)

Exomes 𝑓: 0.040 ( 37 hom. )

Consequence

SMOC1
ENST00000555917.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.257

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]

SMOC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 14-69879273-T-A is Benign according to our data. Variant chr14-69879273-T-A is described in ClinVar as [Benign]. Clinvar id is 1285868.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SMOC1	NM_001034852.3 link	c.-406T>A	upstream_gene_variant	ENST00000361956.8	NP_001030024.1	Q9H4F8-2
SMOC1	NM_001425244.1 link	c.-406T>A	upstream_gene_variant		NP_001412173.1
SMOC1	NM_001425245.1 link	c.-406T>A	upstream_gene_variant		NP_001412174.1
SMOC1	NM_022137.6 link	c.-406T>A	upstream_gene_variant		NP_071420.1	Q9H4F8-1A0A024R6E0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMOC1	ENST00000555917.1 link	n.404+15059T>A	intron_variant	Intron 3 of 3	4
SMOC1	ENST00000361956.8 link	c.-406T>A	upstream_gene_variant		1	NM_001034852.3	ENSP00000355110.4	Q9H4F8-2
SMOC1	ENST00000381280.4 link	c.-406T>A	upstream_gene_variant		1		ENSP00000370680.4	Q9H4F8-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19272

AN:

151844

Hom.:

2880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0569

Gnomad ASJ

AF:

0.0534

Gnomad EAS

AF:

0.0281

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0953

GnomAD4 exome

AF:

0.0398

AC:

606

AN:

15212

Hom.:

AF XY:

0.0404

AC XY:

308

AN XY:

7624

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.0385

Gnomad4 ASJ exome

AF:

0.0474

Gnomad4 EAS exome

AF:

0.0423

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.0240

Gnomad4 NFE exome

AF:

0.0236

Gnomad4 OTH exome

AF:

0.0472

GnomAD4 genome

AF:

0.127

AC:

19315

AN:

151964

Hom.:

2886

Cov.:

AF XY:

0.126

AC XY:

9390

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.0566

Gnomad4 ASJ

AF:

0.0534

Gnomad4 EAS

AF:

0.0284

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.0305

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0942

Alfa

AF:

0.0807

Hom.:

201

Bravo

AF:

0.135

Asia WGS

AF:

0.113

AC:

394

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.0

DANN

Benign

0.72

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over