ENST00000543963.5:c.1833C>T

Variant names:

• chr16-770249-G-A
• rs9745376
• ENST00000543963.5:c.1833C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000543963.5(MSLNL):​c.1833C>T​(p.Asn611Asn) 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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000543963.5. 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
	MIR662	NR_030384.1		n.67G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSLNL	ENST00000543963.5	TSL:5	c.1833C>T	p.Asn611Asn	synonymous	Exon 14 of 15	ENSP00000441381.1
	MIR662	ENST00000384847.1	TSL:6	n.67G>A		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.0141 AC: 3316 AN: 234604 AF XY: 0.0103

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 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

African (AFR) AF: 0.180 AC: 1872 AN: 10402

American (AMR) AF: 0.00985 AC: 353 AN: 35822

Ashkenazi Jewish (ASJ) AF: 0.00104 AC: 12 AN: 11520

East Asian (EAS) AF: 0.000381 AC: 5 AN: 13118

South Asian (SAS) AF: 0.00274 AC: 181 AN: 66144

European-Finnish (FIN) AF: 0.000425 AC: 13 AN: 30616

Middle Eastern (MID) AF: 0.0170 AC: 46 AN: 2710

European-Non Finnish (NFE) AF: 0.00145 AC: 276 AN: 190710

Other (OTH) AF: 0.0101 AC: 166 AN: 16514

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

African (AFR) AF: 0.176 AC: 7289 AN: 41504

American (AMR) AF: 0.0199 AC: 305 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00196 AC: 133 AN: 67994

Other (OTH) AF: 0.0393 AC: 83 AN: 2110

Alfa AF: 0.0432 Hom.: 301

Bravo AF: 0.0587

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.18
DANN	Benign	0.80
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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