rs514385

Variant names:

• chr11-57538538-C-T
• rs514385
• NM_001105565.3:c.-3+896C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105565.3(SMTNL1):​c.-3+896C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,074 control chromosomes in the GnomAD database, including 15,542 homozygotes. 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: 𝑓 0.45 (15542 hom., cov: 33)
• Consequence: SMTNL1 NM_001105565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 14 publications found

Genes affected

SMTNL1 (HGNC:32394): (smoothelin like 1) The protein encoded by this gene is involved in the contraction of both striated and smooth muscle. During pregnancy, the encoded protein interacts with progesterone receptor to attenuate the expression of contractile and metabolic proteins. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105565.3. 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
	SMTNL1	NM_001105565.3	MANE Select	c.-3+896C>T		intron	N/A	NP_001099035.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTNL1	ENST00000527972.6	TSL:5 MANE Select	c.-3+896C>T		intron	N/A	ENSP00000432651.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67677 AN: 151956 Hom.: 15538 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.414

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67697 AN: 152074 Hom.: 15542 Cov.: 33 AF XY: 0.455 AC XY: 33850 AN XY: 74328

African (AFR) AF: 0.403 AC: 16696 AN: 41478

American (AMR) AF: 0.481 AC: 7352 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3813 AN: 5172

South Asian (SAS) AF: 0.495 AC: 2389 AN: 4822

European-Finnish (FIN) AF: 0.533 AC: 5631 AN: 10574

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28700 AN: 67942

Other (OTH) AF: 0.412 AC: 872 AN: 2114

Alfa AF: 0.426 Hom.: 23377

Bravo AF: 0.441

Asia WGS AF: 0.559 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.82
DANN	Benign	0.43
PhyloP100		-0.077

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs514385; hg19: chr11-57306011;