21-39660813-T-C

Variant summary

Our verdict is Benign. Variant got -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. 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 0.70 (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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
B3GALT5	NM_001356336.2	c.254T>C	p.Met85Thr	missense_variant	4/4	ENST00000684187.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALT5	ENST00000684187.2	c.254T>C	p.Met85Thr	missense_variant	4/4		NM_001356336.2	P1
	ENST00000416555.1	n.220+30323T>C		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.760 AC: 179912 AN: 236620 Hom.: 69778 AF XY: 0.769 AC XY: 97986 AN XY: 127380

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 SAS exome AF: 0.794

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

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.782

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.812

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.776

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

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.721

Alfa AF: 0.784 Hom.: 115232

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
MetaRNN	Benign	0.0000011	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N;N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
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

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: rs3746887; hg19: chr21-41032740; COSMIC: COSV58197913;