rs514385

Positions:

• chr11-57538538-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMTNL1	NM_001105565.3	c.-3+896C>T		intron_variant		ENST00000527972.6	NP_001099035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMTNL1	ENST00000527972.6	c.-3+896C>T		intron_variant		5	NM_001105565.3	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

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.412

Alfa AF: 0.426 Hom.: 18544

Bravo AF: 0.441

Asia WGS AF: 0.559 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs514385; hg19: chr11-57306011;