ENST00000509297.6:c.-366T>A

Variant names:

• chr5-136133838-T-A
• rs3764941
• ENST00000509297.6:c.-366T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000509297.6(SMAD5):​c.-366T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 30)
• Consequence: SMAD5 ENST00000509297.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 22 publications found

Genes affected

SMAD5 (HGNC:6771): (SMAD family member 5) The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SMAD5-AS1 (HGNC:30586): (SMAD5 antisense RNA 1) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000277524 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509297.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD5	NM_005903.7	MANE Select	c.-245+876T>A		intron	N/A	NP_005894.3
	SMAD5	NM_001001419.3		c.-329+876T>A		intron	N/A	NP_001001419.1	Q99717
	SMAD5	NM_001001420.3		c.-170+876T>A		intron	N/A	NP_001001420.1	Q99717

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD5	ENST00000509297.6	TSL:1	c.-366T>A		5_prime_UTR	Exon 1 of 8	ENSP00000426696.2	Q99717
	SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.-245+876T>A		intron	N/A	ENSP00000441954.2	Q99717
	SMAD5	ENST00000511116.5	TSL:1	c.-329+876T>A		intron	N/A	ENSP00000424279.1	D6RBB4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 5705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.37
PromoterAI		0.033	Neutral

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

Other links and lift over

dbSNP: rs3764941; hg19: chr5-135469527;