rs3828855

Variant names:

• chr6-41932668-C-T
• rs3828855
• NM_004053.4:c.1276C>T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P426L) has been classified as Uncertain significance.

• 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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BYSL	NM_004053.4	c.1276C>T	p.Pro426Ser	missense_variant	Exon 7 of 7	ENST00000230340.9	NP_004044.3
BYSL	XM_047419281.1	c.1030C>T	p.Pro344Ser	missense_variant	Exon 7 of 7		XP_047275237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BYSL	ENST00000230340.9	c.1276C>T	p.Pro426Ser	missense_variant	Exon 7 of 7	1	NM_004053.4	ENSP00000230340.4

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

GnomAD2 exomes AF: 0.110 AC: 27539 AN: 250748 AF XY: 0.111

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 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

African (AFR) AF: 0.0781 AC: 2613 AN: 33466

American (AMR) AF: 0.0564 AC: 2523 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3121 AN: 26120

East Asian (EAS) AF: 0.171 AC: 6773 AN: 39670

South Asian (SAS) AF: 0.111 AC: 9576 AN: 86238

European-Finnish (FIN) AF: 0.160 AC: 8527 AN: 53376

Middle Eastern (MID) AF: 0.135 AC: 780 AN: 5764

European-Non Finnish (NFE) AF: 0.0977 AC: 108608 AN: 1111394

Other (OTH) AF: 0.106 AC: 6392 AN: 60344

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

African (AFR) AF: 0.0771 AC: 3202 AN: 41538

American (AMR) AF: 0.0620 AC: 948 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3466

East Asian (EAS) AF: 0.163 AC: 844 AN: 5182

South Asian (SAS) AF: 0.105 AC: 507 AN: 4830

European-Finnish (FIN) AF: 0.171 AC: 1820 AN: 10616

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7107 AN: 68006

Other (OTH) AF: 0.101 AC: 213 AN: 2110

Alfa AF: 0.102 Hom.: 2797

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
PhyloP100		1.6
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
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

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