Genetic Variant B4GALNT4:p.Gln38Arg (chr11-369916-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_178537.5(B4GALNT4):c.113A>G(p.Gln38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 976,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

B4GALNT4
NM_178537.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.403

Publications

0 publications found

Variant links:

Genes affected

B4GALNT4 (HGNC:26315): (beta-1,4-N-acetyl-galactosaminyltransferase 4) Enables acetylgalactosaminyltransferase activity. Predicted to be located in Golgi cisterna membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

B4GALNT4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0622966).

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT4	NM_178537.5 link	c.113A>G	p.Gln38Arg	missense_variant	Exon 1 of 20	ENST00000329962.11	NP_848632.2	Q76KP1
B4GALNT4	XR_001747858.2 link	n.418A>G		non_coding_transcript_exon_variant	Exon 1 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT4	ENST00000329962.11 link	c.113A>G	p.Gln38Arg	missense_variant	Exon 1 of 20	1	NM_178537.5	ENSP00000328277.6		Q76KP1
B4GALNT4	ENST00000530717.1 link	n.121A>G		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.000767

AC:

107

AN:

139532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000575

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000633

AC:

AN:

836920

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

386814

show subpopulations

African (AFR)

AF:

0.00265

AC:

AN:

15860

American (AMR)

AF:

0.000954

AC:

AN:

1048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5234

East Asian (EAS)

AF:

0.00

AC:

AN:

3980

South Asian (SAS)

AF:

0.00

AC:

AN:

17360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1830

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

763682

Other (OTH)

AF:

0.000364

AC:

AN:

27482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000760

AC:

106

AN:

139532

Hom.:

Cov.:

AF XY:

0.000594

AC XY:

AN XY:

67362

show subpopulations

African (AFR)

AF:

0.00253

AC:

AN:

38708

American (AMR)

AF:

0.000574

AC:

AN:

13936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.00

AC:

AN:

4728

South Asian (SAS)

AF:

0.00

AC:

AN:

4548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64070

Other (OTH)

AF:

0.00

AC:

AN:

1926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000797

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.113A>G (p.Q38R) alteration is located in exon 1 (coding exon 1) of the B4GALNT4 gene. This alteration results from a A to G substitution at nucleotide position 113, causing the glutamine (Q) at amino acid position 38 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.42

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

PhyloP100

0.40

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

REVEL

Benign

0.062

Sift

Benign

0.065

Sift4G

Benign

0.16

Polyphen

0.036

Vest4

0.17

MVP

0.043

MPC

0.33

ClinPred

0.076

GERP RS

0.68

PromoterAI

0.023

Neutral

(source)

Varity_R

0.12

gMVP

0.42

Mutation Taster

=92/8

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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11-369916-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over