chr21-39660813-T-C

Variant names:

• chr21-39660813-T-C
• rs3746887
• NM_001356336.2:c.254T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001356336.2(B3GALT5):​c.254T>C​(p.Met85Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,593,792 control chromosomes in the GnomAD database, including 497,330 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.

• Frequency:
  • Genomes: 𝑓 0.70 (38910 hom., cov: 31)
  • Exomes 𝑓: 0.79 (458420 hom.)
• Consequence: B3GALT5 NM_001356336.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 43 publications found

Genes affected

B3GALT5 (HGNC:920): (beta-1,3-galactosyltransferase 5) This gene encodes a member of a family of membrane-bound glycoproteins. The encoded protein may synthesize type 1 Lewis antigens, which are elevated in gastrointestinal and pancreatic cancers. Alternatively spliced transcript variants using multiple alternate promoters have been observed for this gene. [provided by RefSeq, Sep 2017]

ENSG00000225330 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1249134E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT5	NM_001356336.2	c.254T>C	p.Met85Thr	missense_variant	Exon 4 of 4	ENST00000684187.2	NP_001343265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALT5	ENST00000684187.2	c.254T>C	p.Met85Thr	missense_variant	Exon 4 of 4		NM_001356336.2	ENSP00000506797.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105969 AN: 151824 Hom.: 38901 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.719

GnomAD2 exomes AF: 0.760 AC: 179912 AN: 236620 AF XY: 0.769

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.766

Gnomad ASJ exome AF: 0.781

Gnomad EAS exome AF: 0.662

Gnomad FIN exome AF: 0.812

Gnomad NFE exome AF: 0.804

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.794 AC: 1145117 AN: 1441850 Hom.: 458420 Cov.: 76 AF XY: 0.796 AC XY: 569134 AN XY: 715138

African (AFR) AF: 0.423 AC: 13908 AN: 32912

American (AMR) AF: 0.760 AC: 32016 AN: 42100

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 19555 AN: 25018

East Asian (EAS) AF: 0.636 AC: 25135 AN: 39498

South Asian (SAS) AF: 0.800 AC: 66090 AN: 82630

European-Finnish (FIN) AF: 0.812 AC: 42871 AN: 52770

Middle Eastern (MID) AF: 0.802 AC: 4542 AN: 5666

European-Non Finnish (NFE) AF: 0.812 AC: 894773 AN: 1101712

Other (OTH) AF: 0.776 AC: 46227 AN: 59544

GnomAD4 genome AF: 0.698 AC: 106005 AN: 151942 Hom.: 38910 Cov.: 31 AF XY: 0.701 AC XY: 52054 AN XY: 74268

African (AFR) AF: 0.445 AC: 18399 AN: 41370

American (AMR) AF: 0.764 AC: 11663 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2713 AN: 3466

East Asian (EAS) AF: 0.650 AC: 3358 AN: 5164

South Asian (SAS) AF: 0.787 AC: 3784 AN: 4810

European-Finnish (FIN) AF: 0.810 AC: 8559 AN: 10570

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 54995 AN: 67982

Other (OTH) AF: 0.721 AC: 1522 AN: 2112

Alfa AF: 0.770 Hom.: 220305

Bravo AF: 0.677

TwinsUK AF: 0.805 AC: 2986

ALSPAC AF: 0.819 AC: 3155

ESP6500AA AF: 0.441 AC: 1943

ESP6500EA AF: 0.810 AC: 6967

ExAC AF: 0.757 AC: 91812

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0010
DANN	Benign	0.45
DEOGEN2	Benign	0.055	T;T;T;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.063	.;.;.;T;T
MetaRNN	Benign	0.0000011	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N;N;N;N;.
PhyloP100		-2.8
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.060	N;.;N;N;.
REVEL	Benign	0.010
Sift	Benign	0.70	T;.;T;T;.
Sift4G	Benign	0.87	T;T;T;T;T
Polyphen		0.0010	B;B;B;B;.
Vest4		0.0080
MPC		0.27
ClinPred		0.00031	T
GERP RS		-5.7
Varity_R		0.034
gMVP		0.53
Mutation Taster		=99/1	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: rs3746887; hg19: chr21-41032740; COSMIC: COSV58197913;