12-57625605-C-T

Variant names:

• chr12-57625605-C-T
• rs114079678
• NM_001478.5:c.*1139G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001478.5(B4GALNT1):​c.*1139G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,591,248 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: B4GALNT1 NM_001478.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.138

Genes affected

B4GALNT1 (HGNC:4117): (beta-1,4-N-acetyl-galactosaminyltransferase 1) GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

ENSG00000287908 (HGNC:):

SLC26A10P (HGNC:14470): (solute carrier family 26 member 10, pseudogene) Predicted to enable anion transmembrane transporter activity. Predicted to be involved in anion transport. Predicted to be active in basolateral plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0071781576).
• BP6: Variant 12-57625605-C-T is Benign according to our data. Variant chr12-57625605-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00118 (179/152208) while in subpopulation AFR AF= 0.00385 (160/41540). AF 95% confidence interval is 0.00336. There are 1 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT1	NM_001478.5	c.*1139G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341156.9	NP_001469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156	c.*1139G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001478.5	ENSP00000341562.4
ENSG00000287908	ENST00000474359.7	n.*1758C>T		non_coding_transcript_exon_variant	Exon 22 of 23	5		ENSP00000431994.2
ENSG00000287908	ENST00000474359.7	n.*1758C>T		3_prime_UTR_variant	Exon 22 of 23	5		ENSP00000431994.2

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 174 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

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

GnomAD3 exomes AF: 0.000320 AC: 74 AN: 231394 Hom.: 0 AF XY: 0.000177 AC XY: 22 AN XY: 123974

Gnomad AFR exome AF: 0.00391

Gnomad AMR exome AF: 0.000338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.000126 AC: 182 AN: 1439040 Hom.: 1 Cov.: 38 AF XY: 0.000109 AC XY: 78 AN XY: 713144

Gnomad4 AFR exome AF: 0.00360

Gnomad4 AMR exome AF: 0.000304

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.0000487

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000155

Gnomad4 OTH exome AF: 0.000404

GnomAD4 genome AF: 0.00118 AC: 179 AN: 152208 Hom.: 1 Cov.: 32 AF XY: 0.00112 AC XY: 83 AN XY: 74414

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.00139

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000362 AC: 44

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC26A10P: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.040	D
Polyphen		0.17	B
Vest4		0.074
MVP		0.70
MPC		0.15
ClinPred		0.031	T
GERP RS		1.3
Varity_R		0.081
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs114079678; hg19: chr12-58019388;