Genetic Variant MSLNL:p.Asn611Lys (chr16-770249-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000543963.5(MSLNL):c.1833C>A(p.Asn611Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict 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: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSLNL
ENST00000543963.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.833

Publications

11 publications found

Variant links:

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]

MSLNL links:

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]

MIR662 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38268927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIR662	NR_030384.1 link	n.67G>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR662	unassigned_transcript_2766	n.7G>T	non_coding_transcript_exon_variant	Exon 1 of 1
MSLNL		n.770249G>T	intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSLNL	ENST00000543963.5 link	c.1833C>A	p.Asn611Lys	missense_variant	Exon 14 of 15	5		ENSP00000441381.1		H0YG18
MIR662	ENST00000384847.1 link	n.67G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

377584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

215086

African (AFR)

AF:

0.00

AC:

AN:

10422

American (AMR)

AF:

0.00

AC:

AN:

35822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11520

East Asian (EAS)

AF:

0.00

AC:

AN:

13118

South Asian (SAS)

AF:

0.00

AC:

AN:

66144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

190712

Other (OTH)

AF:

0.00

AC:

AN:

16518

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.0

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.1

PhyloP100

-0.83

PROVEAN

Uncertain

-4.3

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.67

MutPred

0.62

.;Gain of ubiquitination at N561 (P = 0.0238);

MVP

0.067

ClinPred

0.98

GERP RS

-4.7

Varity_R

0.48

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over