13-36845112-GTGTATA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001127217.3(SMAD9):c.*3558_*3563del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.031 (42 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: SMAD9 NM_001127217.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.639

Genes affected

SMAD9 (HGNC:6774): (SMAD family member 9) The protein encoded by this gene is a member of the SMAD family, which transduces signals from TGF-beta family members. The encoded protein is activated by bone morphogenetic proteins and interacts with SMAD4. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.*3558_*3563del		3_prime_UTR_variant	7/7	ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5	c.*3558_*3563del		3_prime_UTR_variant	7/7	5	NM_001127217.3	P1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 2153 AN: 70744 Hom.: 42 Cov.: 0

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00336

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00216

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.0273

Gnomad NFE AF: 0.00461

Gnomad OTH AF: 0.0193

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

GnomAD4 genome AF: 0.0306 AC: 2169 AN: 70774 Hom.: 42 Cov.: 0 AF XY: 0.0313 AC XY: 1073 AN XY: 34308

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00336

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00218

Gnomad4 FIN AF: 0.0294

Gnomad4 NFE AF: 0.00461

Gnomad4 OTH AF: 0.0191

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Pulmonary hypertension, primary, 1 Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757843262; hg19: chr13-37419249;