Genetic Variant NM_001356336.2:c.254T>C (chr21-39660813-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

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: 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 link	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 link	c.254T>C	p.Met85Thr	missense_variant	Exon 4 of 4		NM_001356336.2	ENSP00000506797.1		Q9Y2C3

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

105969

AN:

151824

Hom.:

38901

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.796

AC XY:

569134

AN XY:

715138

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

14184

28368

42552

56736

70920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20764

41528

62292

83056

103820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.698

AC:

106005

AN:

151942

Hom.:

38910

Cov.:

AF XY:

0.701

AC XY:

52054

AN XY:

74268

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1474

2947

4421

5894

7368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0010

(source)

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

LIST_S2

Benign

0.063

.;.;.;T;T

MetaRNN

Benign

0.0000011

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

N;N;N;N;.

PhyloP100

-2.8

PrimateAI

Benign

0.23

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

GERP RS

-5.7

Varity_R

0.034

gMVP

0.53

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over