Genetic Variant NM_178537.5:c.656C>T (chr11-373468-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_178537.5(B4GALNT4):c.656C>T(p.Ala219Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,553,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

B4GALNT4
NM_178537.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT4	NM_178537.5 link	c.656C>T	p.Ala219Val	missense_variant	Exon 7 of 20	ENST00000329962.11	NP_848632.2	Q76KP1
B4GALNT4	XM_017017654.2 link	c.380C>T	p.Ala127Val	missense_variant	Exon 7 of 20		XP_016873143.1
B4GALNT4	XR_001747858.2 link	n.961C>T		non_coding_transcript_exon_variant	Exon 7 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT4	ENST00000329962.11 link	c.656C>T	p.Ala219Val	missense_variant	Exon 7 of 20	1	NM_178537.5	ENSP00000328277.6		Q76KP1

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

143916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000150

Gnomad OTH

AF:

0.000498

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249468

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000362

AC:

AN:

1409964

Hom.:

Cov.:

AF XY:

0.0000342

AC XY:

AN XY:

701120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31328

American (AMR)

AF:

0.00

AC:

AN:

43380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24108

East Asian (EAS)

AF:

0.0000322

AC:

AN:

31070

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47750

Middle Eastern (MID)

AF:

0.000367

AC:

AN:

5450

European-Non Finnish (NFE)

AF:

0.0000424

AC:

AN:

1083966

Other (OTH)

AF:

0.0000175

AC:

AN:

57186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000139

AC:

AN:

143916

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

69728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38372

American (AMR)

AF:

0.00

AC:

AN:

14168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

4510

South Asian (SAS)

AF:

0.00

AC:

AN:

4364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66570

Other (OTH)

AF:

0.000498

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.656C>T (p.A219V) alteration is located in exon 7 (coding exon 7) of the B4GALNT4 gene. This alteration results from a C to T substitution at nucleotide position 656, causing the alanine (A) at amino acid position 219 to be replaced by a valine (V). 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

Pathogenic

0.71

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.083

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

5.5

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.27

Sift

Benign

0.035

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.62

MutPred

0.66

Loss of disorder (P = 0.0712);

MVP

0.29

MPC

0.98

ClinPred

0.96

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.76

Mutation Taster

=55/45

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_178537.5:c.656C>T

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