chr13-36845100-ATGTG-A

Position:

• chr13-36845100-ATGTG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001127217.3(SMAD9):​c.*3572_*3575del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 145,890 control chromosomes in the GnomAD database, including 232 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (232 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMAD9 NM_001127217.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.685

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 -10 ACMG points.

• BP6: Variant 13-36845100-ATGTG-A is Benign according to our data. Variant chr13-36845100-ATGTG-A is described in ClinVar as [Benign]. Clinvar id is 311817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.*3572_*3575del		3_prime_UTR_variant	7/7	ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5	c.*3572_*3575del		3_prime_UTR_variant	7/7	5	NM_001127217.3	P1

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5304 AN: 145782 Hom.: 231 Cov.: 30

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.00792

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00336

Gnomad OTH AF: 0.0180

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0365 AC: 5320 AN: 145890 Hom.: 232 Cov.: 30 AF XY: 0.0384 AC XY: 2727 AN XY: 71054

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.00336

Gnomad4 OTH AF: 0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pulmonary hypertension, primary, 1 Benign:1

Benign, 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: rs201352307; hg19: chr13-37419237;