rs79733377

Variant names:

• chr13-36867311-G-A
• NM_001127217.3:c.743C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-36867311-G-A
• chr13-36867311-G-C
• chr13-36867311-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_001127217.3(SMAD9):​c.743C>T​(p.Thr248Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000715 in 1,398,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: SMAD9 NM_001127217.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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 -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15600702).
• BS2: High AC in GnomAdExome4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD9	NM_001127217.3	c.743C>T	p.Thr248Ile	missense_variant	Exon 4 of 7	ENST00000379826.5	NP_001120689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD9	ENST00000379826.5	c.743C>T	p.Thr248Ile	missense_variant	Exon 4 of 7	5	NM_001127217.3	ENSP00000369154.4
SMAD9	ENST00000350148.10	c.671-1553C>T		intron_variant	Intron 3 of 5	1		ENSP00000239885.6
SMAD9	ENST00000399275.7	n.*381-1553C>T		intron_variant	Intron 3 of 5	1		ENSP00000382216.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000715 AC: 10 AN: 1398850 Hom.: 0 Cov.: 29 AF XY: 0.00000725 AC XY: 5 AN XY: 689958

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000834

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.66
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.39	.;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.67	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.89	N;N
REVEL	Benign	0.27
Sift	Benign	0.15	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0	B;B
Vest4		0.069
MutPred		0.37		Gain of catalytic residue at V253 (P = 0.0045);Gain of catalytic residue at V253 (P = 0.0045);
MVP		0.93
MPC		0.24
ClinPred		0.066	T
GERP RS		2.6
Varity_R		0.042
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-37441448;