rs886051379

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005902.4(SMAD3):​c.-100C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Consequence

SMAD3
NM_005902.4 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.199
Variant links:
Genes affected
SMAD3 (HGNC:6769): (SMAD family member 3) The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMAD3NM_005902.4 linkc.-100C>A 5_prime_UTR_variant Exon 1 of 9 ENST00000327367.9 NP_005893.1 P84022-1A0A024R5Z3Q9P0T0
SMAD3NM_001407011.1 linkc.-100C>A 5_prime_UTR_variant Exon 1 of 10 NP_001393940.1
SMAD3NM_001407012.1 linkc.-100C>A 5_prime_UTR_variant Exon 1 of 8 NP_001393941.1
SMAD3NM_001407013.1 linkc.-100C>A 5_prime_UTR_variant Exon 1 of 8 NP_001393942.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMAD3ENST00000327367 linkc.-100C>A 5_prime_UTR_variant Exon 1 of 9 1 NM_005902.4 ENSP00000332973.4 P84022-1
SMAD3ENST00000560424 linkc.-100C>A 5_prime_UTR_variant Exon 1 of 10 3 ENSP00000455540.2 H3BQ00
SMAD3ENST00000559460.6 linkc.-110+2111C>A intron_variant Intron 1 of 8 4 ENSP00000453082.2 H0YL71

Frequencies

GnomAD3 genomes
AF:
0.00000663
AC:
1
AN:
150750
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
8
GnomAD4 genome
AF:
0.00000663
AC:
1
AN:
150750
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73594
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
12
DANN
Benign
0.89

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.

Other links and lift over

dbSNP: rs886051379; hg19: chr15-67358393; API