14-69879699-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.379

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]

ACMG classification

Verdict is Benign. Variant got -15 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.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 190 AN: 152190 Hom.: 0 Cov.: 33

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.: 1 AF XY: 0.00118 AC XY: 128 AN XY: 108536

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.: 3 Cov.: 31 AF XY: 0.00166 AC XY: 1178 AN XY: 708748

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.: 0 Cov.: 33 AF XY: 0.00126 AC XY: 94 AN XY: 74480

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.: 0

Bravo AF: 0.000835

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	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	13
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

Other links and lift over

dbSNP: rs138862255; hg19: chr14-70346416;