rs61753157

Variant names:

• chr13-36872841-C-A
• NM_001127217.3:c.487G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-36872841-C-A
• chr13-36872841-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127217.3(SMAD9):​c.487G>T​(p.Ala163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A163T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMAD9 NM_001127217.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15393844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD9	NM_001127217.3	c.487G>T	p.Ala163Ser	missense_variant	Exon 3 of 7	ENST00000379826.5	NP_001120689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD9	ENST00000379826.5	c.487G>T	p.Ala163Ser	missense_variant	Exon 3 of 7	5	NM_001127217.3	ENSP00000369154.4
SMAD9	ENST00000350148.10	c.487G>T	p.Ala163Ser	missense_variant	Exon 3 of 6	1		ENSP00000239885.6
SMAD9	ENST00000399275.7	n.*197G>T		non_coding_transcript_exon_variant	Exon 3 of 6	1		ENSP00000382216.3
SMAD9	ENST00000399275.7	n.*197G>T		3_prime_UTR_variant	Exon 3 of 6	1		ENSP00000382216.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.25	T;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	.;D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.19	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.77	T;T;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.34
MutPred		0.31		Gain of catalytic residue at E168 (P = 0.0086);Gain of catalytic residue at E168 (P = 0.0086);Gain of catalytic residue at E168 (P = 0.0086);
MVP		0.90
MPC		0.22
ClinPred		0.29	T
GERP RS		3.7
Varity_R		0.029
gMVP		0.35

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: chr13-37446978;