Genetic Variant B3GALT5:p.Met85Arg (chr21-39660813-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001356336.2(B3GALT5):c.254T>G(p.Met85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

B3GALT5
NM_001356336.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

43 publications found

Variant links:

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]

B3GALT5 links:

ENSG00000225330 (HGNC:):

ENSG00000225330 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03122583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001356336.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GALT5	NM_001356336.2	MANE Select	c.254T>G	p.Met85Arg	missense	Exon 4 of 4	NP_001343265.1	Q9Y2C3
B3GALT5	NM_033172.3		c.266T>G	p.Met89Arg	missense	Exon 3 of 3	NP_149362.2	A0A0A0MS93
B3GALT5	NM_001278650.2		c.254T>G	p.Met85Arg	missense	Exon 3 of 3	NP_001265579.1	Q9Y2C3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GALT5	ENST00000684187.2	MANE Select	c.254T>G	p.Met85Arg	missense	Exon 4 of 4	ENSP00000506797.1	Q9Y2C3
B3GALT5	ENST00000380618.5	TSL:1	c.254T>G	p.Met85Arg	missense	Exon 3 of 3	ENSP00000369992.1	Q9Y2C3
B3GALT5	ENST00000380620.8	TSL:1	c.254T>G	p.Met85Arg	missense	Exon 5 of 5	ENSP00000369994.3	Q9Y2C3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1442258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715372

African (AFR)

AF:

0.00

AC:

AN:

32930

American (AMR)

AF:

0.00

AC:

AN:

42180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25050

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.00

AC:

AN:

82700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101876

Other (OTH)

AF:

0.00

AC:

AN:

59558

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

220305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0020

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.12

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.14

M_CAP

Benign

0.0069

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.57

PhyloP100

-2.8

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.8

REVEL

Benign

0.024

Sift

Benign

0.51

Sift4G

Benign

0.55

Polyphen

0.0040

Vest4

0.066

MutPred

0.37

Gain of solvent accessibility (P = 0.039)

MVP

0.030

MPC

0.35

ClinPred

0.040

GERP RS

-5.7

Varity_R

0.20

gMVP

0.72

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over