NM_134269.3:c.-4C>T

Variant names:

• chr22-31083255-C-T
• rs772039810
• NM_134269.3:c.-4C>T

Variant summary

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

The NM_134269.3(SMTN):​c.-4C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,445,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SMTN NM_134269.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 1 publications found

Genes affected

SMTN (HGNC:11126): (smoothelin) This gene encodes a structural protein that is found exclusively in contractile smooth muscle cells. It associates with stress fibers and constitutes part of the cytoskeleton. This gene is localized to chromosome 22q12.3, distal to the TUPLE1 locus and outside the DiGeorge syndrome deletion. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2011]

ENSG00000273387 (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=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134269.3. 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
	SMTN	NM_134269.3	MANE Select	c.-4C>T		5_prime_UTR	Exon 2 of 21	NP_599031.1	P53814-5
	SMTN	NM_001382642.1		c.279C>T	p.Ser93Ser	synonymous	Exon 4 of 23	NP_001369571.1
	SMTN	NM_001207017.1		c.159C>T	p.Ser53Ser	synonymous	Exon 2 of 21	NP_001193946.1	A0A087X1R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	ENST00000333137.12	TSL:1 MANE Select	c.-4C>T		5_prime_UTR	Exon 2 of 21	ENSP00000329532.7	P53814-5
	SMTN	ENST00000347557.6	TSL:1	c.-4C>T		5_prime_UTR	Exon 2 of 20	ENSP00000328635.5	P53814-1
	SMTN	ENST00000619644.5	TSL:2	c.159C>T	p.Ser53Ser	synonymous	Exon 2 of 21	ENSP00000484398.1	A0A087X1R1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000893 AC: 2 AN: 223956 AF XY: 0.00000831

Gnomad AFR exome AF: 0.0000697

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000616

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000159 AC: 23 AN: 1445618 Hom.: 0 Cov.: 31 AF XY: 0.0000195 AC XY: 14 AN XY: 717542

African (AFR) AF: 0.0000300 AC: 1 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 40976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25690

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39026

South Asian (SAS) AF: 0.00 AC: 0 AN: 83050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4728

European-Non Finnish (NFE) AF: 0.0000181 AC: 20 AN: 1106620

Other (OTH) AF: 0.0000167 AC: 1 AN: 59804

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
DANN	Benign	0.84
PhyloP100		-0.17
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs772039810; hg19: chr22-31479241;