13-36845114-GTATA-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001127217.3(SMAD9):c.*3558_*3561del 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 0.00054 (1 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: SMAD9 NM_001127217.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.*3558_*3561del		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_*3561del		3_prime_UTR_variant	7/7	5	NM_001127217.3	P1

Frequencies

GnomAD3 genomes AF: 0.000531 AC: 47 AN: 88582 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000623

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000193

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000727

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000542 AC: 48 AN: 88590 Hom.: 1 Cov.: 0 AF XY: 0.000509 AC XY: 22 AN XY: 43180

Gnomad4 AFR AF: 0.000622

Gnomad4 AMR AF: 0.000289

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000728

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00110

Gnomad4 NFE AF: 0.000558

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pulmonary hypertension, primary, 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs71084449; hg19: chr13-37419251;