rs172899

Variant names:

• chr14-69924799-G-C
• rs172899
• NM_001034852.3:c.100-27339G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001034852.3(SMOC1):​c.100-27339G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.29
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

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.100-27339G>C		intron	N/A	NP_001030024.1	Q9H4F8-2
	SMOC1	NM_001425244.1		c.100-27339G>C		intron	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.100-27339G>C		intron	N/A	NP_001412174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.100-27339G>C		intron	N/A	ENSP00000355110.4	Q9H4F8-2
	SMOC1	ENST00000381280.4	TSL:1	c.100-27339G>C		intron	N/A	ENSP00000370680.4	Q9H4F8-1
	SMOC1	ENST00000853906.1		c.100-27339G>C		intron	N/A	ENSP00000523965.1

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 5 AN: 3828 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00385

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00350

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000887

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00130 AC: 5 AN: 3850 Hom.: 0 Cov.: 0 AF XY: 0.00147 AC XY: 3 AN XY: 2036

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 436

American (AMR) AF: 0.00385 AC: 1 AN: 260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 80

East Asian (EAS) AF: 0.00 AC: 0 AN: 68

South Asian (SAS) AF: 0.00 AC: 0 AN: 114

European-Finnish (FIN) AF: 0.00350 AC: 2 AN: 572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.000887 AC: 2 AN: 2256

Other (OTH) AF: 0.00 AC: 0 AN: 32

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00105395), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0767 Hom.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.22
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism

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: rs172899; hg19: chr14-70391516;