Genetic Variant NM_001034852.3:c.718C>A (chr14-70010807-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001034852.3(SMOC1):c.718C>A(p.Gln240Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

SMOC1
NM_001034852.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.00

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20383108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC1	NM_001034852.3 link	c.718C>A	p.Gln240Lys	missense_variant	Exon 8 of 12	ENST00000361956.8	NP_001030024.1	Q9H4F8-2
SMOC1	NM_001425244.1 link	c.751C>A	p.Gln251Lys	missense_variant	Exon 8 of 12		NP_001412173.1
SMOC1	NM_001425245.1 link	c.751C>A	p.Gln251Lys	missense_variant	Exon 8 of 12		NP_001412174.1
SMOC1	NM_022137.6 link	c.718C>A	p.Gln240Lys	missense_variant	Exon 8 of 12		NP_071420.1	Q9H4F8-1A0A024R6E0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMOC1	ENST00000361956.8 link	c.718C>A	p.Gln240Lys	missense_variant	Exon 8 of 12	1	NM_001034852.3	ENSP00000355110.4	Q9H4F8-2
SMOC1	ENST00000381280.4 link	c.718C>A	p.Gln240Lys	missense_variant	Exon 8 of 12	1		ENSP00000370680.4	Q9H4F8-1
SMOC1	ENST00000557483.1 link	n.296C>A		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251438

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000451

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000666

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.16

.;T

Eigen

Benign

-0.081

Eigen_PC

Benign

0.082

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.11

Sift

Benign

0.069

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.36

B;B

Vest4

0.16

MVP

0.77

MPC

0.67

ClinPred

0.068

GERP RS

5.5

Varity_R

0.24

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over