11-372126-A-G

Variant names:

• chr11-372126-A-G
• rs753662463
• NM_178537.5:c.169A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_178537.5(B4GALNT4):​c.169A>G​(p.Ser57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,549,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: B4GALNT4 NM_178537.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0830
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017289788).
• BP6: Variant 11-372126-A-G is Benign according to our data. Variant chr11-372126-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2261380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 52 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT4	NM_178537.5	c.169A>G	p.Ser57Gly	missense_variant	Exon 2 of 20	ENST00000329962.11	NP_848632.2
B4GALNT4	XR_001747858.2	n.474A>G		non_coding_transcript_exon_variant	Exon 2 of 18
B4GALNT4	XM_017017654.2	c.-108A>G		5_prime_UTR_variant	Exon 2 of 20		XP_016873143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT4	ENST00000329962.11	c.169A>G	p.Ser57Gly	missense_variant	Exon 2 of 20	1	NM_178537.5	ENSP00000328277.6
B4GALNT4	ENST00000530717.1	n.177A>G		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000109 AC: 17 AN: 155822 AF XY: 0.000146

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000372 AC: 52 AN: 1397176 Hom.: 0 Cov.: 31 AF XY: 0.0000522 AC XY: 36 AN XY: 689096

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.000619 AC: 49 AN: 79202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078758

Other (OTH) AF: 0.0000518 AC: 3 AN: 57904

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.000107 AC: 3

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 15, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.76
DANN	Benign	0.65
DEOGEN2	Benign	0.00081	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-0.083
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.14		Loss of phosphorylation at S57 (P = 0.038);
MVP		0.068
MPC		0.27
ClinPred		0.023	T
GERP RS		0.47
Varity_R		0.037
gMVP		0.13
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs753662463; hg19: chr11-372126;