rs3828855

chr6-41932668-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004053.4(BYSL):c.1276C>T(p.Pro426Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,320 control chromosomes in the GnomAD database, including 8,959 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (860 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8099 hom.)
• Consequence: BYSL NM_004053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019687116).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BYSL	NM_004053.4	c.1276C>T	p.Pro426Ser	missense_variant	7/7	ENST00000230340.9
BYSL	XM_047419281.1	c.1030C>T	p.Pro344Ser	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BYSL	ENST00000230340.9	c.1276C>T	p.Pro426Ser	missense_variant	7/7	1	NM_004053.4	P1
BYSL	ENST00000372996.2	c.*421C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	5
BYSL	ENST00000489290.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15199 AN: 152128 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.110 AC: 27539 AN: 250748 Hom.: 1657 AF XY: 0.111 AC XY: 15095 AN XY: 135528

Gnomad AFR exome AF: 0.0770

Gnomad AMR exome AF: 0.0556

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.165

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.102 AC: 148913 AN: 1461076 Hom.: 8099 Cov.: 31 AF XY: 0.102 AC XY: 74314 AN XY: 726688

Gnomad4 AFR exome AF: 0.0781

Gnomad4 AMR exome AF: 0.0564

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.0977

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0997 AC: 15186 AN: 152244 Hom.: 860 Cov.: 32 AF XY: 0.102 AC XY: 7609 AN XY: 74440

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.0620

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.101

Alfa AF: 0.104 Hom.: 2123

Bravo AF: 0.0908

TwinsUK AF: 0.0971 AC: 360

ALSPAC AF: 0.0950 AC: 366

ESP6500AA AF: 0.0828 AC: 365

ESP6500EA AF: 0.109 AC: 935

ExAC AF: 0.114 AC: 13819

Asia WGS AF: 0.143 AC: 494 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	19
Dann	Benign	0.61
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.3	N
MutationTaster	Benign	0.85	P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.016
MPC		0.36
ClinPred		0.0069	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.072

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

Other links and lift over

dbSNP: rs3828855; hg19: chr6-41900406; COSMIC: COSV57827792; COSMIC: COSV57827792;