chr6-41930157-G-A

Variant names:

• chr6-41930157-G-A
• NM_004053.4:c.457G>A

Variant summary

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

The NM_004053.4(BYSL):​c.457G>A​(p.Glu153Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BYSL NM_004053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.81

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 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	c.457G>A	p.Glu153Lys	missense_variant	Exon 3 of 7	ENST00000230340.9	NP_004044.3
BYSL	XM_047419281.1	c.211G>A	p.Glu71Lys	missense_variant	Exon 3 of 7		XP_047275237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BYSL	ENST00000230340.9	c.457G>A	p.Glu153Lys	missense_variant	Exon 3 of 7	1	NM_004053.4	ENSP00000230340.4
BYSL	ENST00000372996.2	n.127G>A		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000362087.2
BYSL	ENST00000475702.1	n.470G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
BYSL	ENST00000489290.1	n.432-478G>A		intron_variant	Intron 2 of 5	3		ENSP00000417813.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.056	T
Polyphen		0.064	B
Vest4		0.65
MutPred		0.57		Gain of MoRF binding (P = 0.0043);
MVP		0.62
MPC		0.45
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.62
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-41897895;