rs9745376

Positions:

• chr16-770249-G-A
• chr16-770249-G-C
• chr16-770249-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000543963.5(MSLNL):​c.1833C>T​(p.Asn611=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 529,760 control chromosomes in the GnomAD database, including 815 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 0.051 (638 hom., cov: 34)
  • Exomes 𝑓: 0.0077 (177 hom.)
• Consequence: MSLNL ENST00000543963.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833

Genes affected

MSLNL (HGNC:14170): (mesothelin like) Predicted to be involved in cell-matrix adhesion. Predicted to be located in membrane. Predicted to be integral component of membrane. Predicted to be active in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

MIR662 (HGNC:32918): (microRNA 662) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.833 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR662	NR_030384.1	n.67G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSLNL	ENST00000543963.5	c.1833C>T	p.Asn611=	synonymous_variant	14/15	5		P1
MIR662	ENST00000384847.1	n.67G>A		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7800 AN: 152088 Hom.: 631 Cov.: 34

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00196

Gnomad OTH AF: 0.0398

GnomAD3 exomes AF: 0.0141 AC: 3316 AN: 234604 Hom.: 212 AF XY: 0.0103 AC XY: 1328 AN XY: 128506

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.00985

Gnomad ASJ exome AF: 0.00158

Gnomad EAS exome AF: 0.000389

Gnomad SAS exome AF: 0.00265

Gnomad FIN exome AF: 0.000584

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.00646

GnomAD4 exome AF: 0.00774 AC: 2924 AN: 377556 Hom.: 177 Cov.: 0 AF XY: 0.00598 AC XY: 1287 AN XY: 215072

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.00985

Gnomad4 ASJ exome AF: 0.00104

Gnomad4 EAS exome AF: 0.000381

Gnomad4 SAS exome AF: 0.00274

Gnomad4 FIN exome AF: 0.000425

Gnomad4 NFE exome AF: 0.00145

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0515 AC: 7836 AN: 152204 Hom.: 638 Cov.: 34 AF XY: 0.0499 AC XY: 3715 AN XY: 74402

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0181 Hom.: 109

Bravo AF: 0.0587

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.18
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9745376; hg19: chr16-820249; COSMIC: COSV53499492; COSMIC: COSV53499492;