Variant 14-69879699-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001034852.3(SMOC1):c.21C>T(p.Ala7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,578,372 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

SMOC1
NM_001034852.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.379

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 14-69879699-C-T is Benign according to our data. Variant chr14-69879699-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 778483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.379 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00125 (190/152306) while in subpopulation NFE AF= 0.00181 (123/68002). AF 95% confidence interval is 0.00155. There are 0 homozygotes in gnomad4. There are 94 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMOC1	NM_001034852.3 linkuse as main transcript	c.21C>T	p.Ala7=	synonymous_variant	1/12	ENST00000361956.8
SMOC1	NM_022137.6 linkuse as main transcript	c.21C>T	p.Ala7=	synonymous_variant	1/12
SMOC1	XM_005267995.2 linkuse as main transcript	c.21C>T	p.Ala7=	synonymous_variant	1/12
SMOC1	XM_005267996.2 linkuse as main transcript	c.21C>T	p.Ala7=	synonymous_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8 linkuse as main transcript	c.21C>T	p.Ala7=	synonymous_variant	1/12	1	NM_001034852.3	A2	Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.21C>T	p.Ala7=	synonymous_variant	1/12	1		P4	Q9H4F8-1
SMOC1	ENST00000555917.1 linkuse as main transcript	n.404+15485C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00181

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00123

AC:

238

AN:

193996

Hom.:

AF XY:

0.00118

AC XY:

128

AN XY:

108536

show subpopulations

Gnomad AFR exome

AF:

0.000191

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00303

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000898

Gnomad FIN exome

AF:

0.00226

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.00162

GnomAD4 exome

AF:

0.00174

AC:

2478

AN:

1426066

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1178

AN XY:

708748

show subpopulations

Gnomad4 AFR exome

AF:

0.000156

Gnomad4 AMR exome

AF:

0.000236

Gnomad4 ASJ exome

AF:

0.00297

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000894

Gnomad4 FIN exome

AF:

0.00271

Gnomad4 NFE exome

AF:

0.00194

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152306

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.000835

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	SMOC1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 13, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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.

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