rs3825739

Variant names:

• chr14-70010791-C-T
• rs3825739
• NM_001034852.3:c.702C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-70010791-C-T
• chr14-70010791-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001034852.3(SMOC1):​c.702C>T​(p.Ala234Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,613,988 control chromosomes in the GnomAD database, including 32,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2684 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29609 hom.)
• Consequence: SMOC1 NM_001034852.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0660
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• microphthalmia with limb anomalies

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-70010791-C-T is Benign according to our data. Variant chr14-70010791-C-T is described in ClinVar as Benign. ClinVar VariationId is 257189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.066 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	NM_001034852.3	MANE Select	c.702C>T	p.Ala234Ala	synonymous	Exon 8 of 12	NP_001030024.1	Q9H4F8-2
	SMOC1	NM_001425244.1		c.735C>T	p.Ala245Ala	synonymous	Exon 8 of 12	NP_001412173.1
	SMOC1	NM_001425245.1		c.735C>T	p.Ala245Ala	synonymous	Exon 8 of 12	NP_001412174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.702C>T	p.Ala234Ala	synonymous	Exon 8 of 12	ENSP00000355110.4	Q9H4F8-2
	SMOC1	ENST00000381280.4	TSL:1	c.702C>T	p.Ala234Ala	synonymous	Exon 8 of 12	ENSP00000370680.4	Q9H4F8-1
	SMOC1	ENST00000853906.1		c.750C>T	p.Ala250Ala	synonymous	Exon 9 of 13	ENSP00000523965.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24239 AN: 152100 Hom.: 2677 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.173

GnomAD2 exomes AF: 0.211 AC: 53137 AN: 251426 AF XY: 0.208

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.412

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.193 AC: 282601 AN: 1461770 Hom.: 29609 Cov.: 35 AF XY: 0.194 AC XY: 140832 AN XY: 727186

African (AFR) AF: 0.0339 AC: 1134 AN: 33480

American (AMR) AF: 0.337 AC: 15075 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3860 AN: 26136

East Asian (EAS) AF: 0.409 AC: 16227 AN: 39700

South Asian (SAS) AF: 0.202 AC: 17406 AN: 86258

European-Finnish (FIN) AF: 0.169 AC: 9022 AN: 53410

Middle Eastern (MID) AF: 0.108 AC: 623 AN: 5768

European-Non Finnish (NFE) AF: 0.187 AC: 207741 AN: 1111904

Other (OTH) AF: 0.191 AC: 11513 AN: 60390

GnomAD4 genome AF: 0.159 AC: 24249 AN: 152218 Hom.: 2684 Cov.: 32 AF XY: 0.165 AC XY: 12262 AN XY: 74434

African (AFR) AF: 0.0408 AC: 1697 AN: 41560

American (AMR) AF: 0.272 AC: 4168 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2088 AN: 5166

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4820

European-Finnish (FIN) AF: 0.186 AC: 1970 AN: 10604

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12298 AN: 67982

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.171 Hom.: 8559

Bravo AF: 0.162

Asia WGS AF: 0.254 AC: 880 AN: 3478

EpiCase AF: 0.172

EpiControl AF: 0.168

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Microphthalmia with limb anomalies (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		-0.066
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3825739; hg19: chr14-70477508; COSMIC: COSV62761187;