Genetic Variant BYSL:p.Arg189Leu (chr6-41930266-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004053.4(BYSL):c.566G>T(p.Arg189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,678 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

BYSL
NM_004053.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

BYSL (HGNC:1157): (bystin like) Bystin is expressed as a 2-kb major transcript and a 3.6-kb minor transcript in SNG-M cells and in human trophoblastic teratocarcinoma HT-H cells. Protein binding assays determined that bystin binds directly to trophinin and tastin, and that binding is enhanced when cytokeratins 8 and 18 are present. Immunocytochemistry of HT-H cells showed that bystin colocalizes with trophinin, tastin, and the cytokeratins, suggesting that these molecules form a complex in trophectoderm cells at the time of implantation. Using immunohistochemistry it was determined that trophinin and bystin are found in the placenta from the sixth week of pregnancy. Both proteins were localized in the cytoplasm of the syncytiotrophoblast in the chorionic villi and in endometrial decidual cells at the uteroplacental interface. After week 10, the levels of trophinin, tastin, and bystin decreased and then disappeared from placental villi. [provided by RefSeq, Jul 2008]

BYSL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BYSL	NM_004053.4 link	c.566G>T	p.Arg189Leu	missense_variant	Exon 3 of 7	ENST00000230340.9	NP_004044.3	Q13895
BYSL	XM_047419281.1 link	c.320G>T	p.Arg107Leu	missense_variant	Exon 3 of 7		XP_047275237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BYSL	ENST00000230340.9 link	c.566G>T	p.Arg189Leu	missense_variant	Exon 3 of 7	1	NM_004053.4	ENSP00000230340.4	Q13895
BYSL	ENST00000372996.2 link	n.236G>T		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000362087.2	H7BY94
BYSL	ENST00000475702.1 link	n.579G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
BYSL	ENST00000489290.1 link	n.432-369G>T		intron_variant	Intron 2 of 5	3		ENSP00000417813.1	F8WBL2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000194

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0063

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.16

Sift

Benign

0.11

Sift4G

Benign

0.070

Polyphen

0.15

Vest4

0.70

MVP

0.61

MPC

0.45

ClinPred

0.97

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.21

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over