13-36845114-G-GTA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001127217.3(SMAD9):c.*3561_*3562insTA 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 0.0058 (2 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: 0.0650

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 -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00584 (518/88644) while in subpopulation EAS AF= 0.0164 (45/2744). AF 95% confidence interval is 0.0131. There are 2 homozygotes in gnomad4. There are 248 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd at 517 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.*3561_*3562insTA		3_prime_UTR_variant	7/7	ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5	c.*3561_*3562insTA		3_prime_UTR_variant	7/7	5	NM_001127217.3	P1

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 517 AN: 88634 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00250

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.00761

Gnomad FIN AF: 0.000821

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00393

Gnomad OTH AF: 0.00488

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00584 AC: 518 AN: 88644 Hom.: 2 Cov.: 0 AF XY: 0.00574 AC XY: 248 AN XY: 43198

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00250

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.00763

Gnomad4 FIN AF: 0.000821

Gnomad4 NFE AF: 0.00393

Gnomad4 OTH AF: 0.00487

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

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;