chr12-57625419-C-T

Position:

• chr12-57625419-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001478.5(B4GALNT1):​c.*1325G>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 0.00267 in 1,614,136 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (13 hom.)
• Consequence: B4GALNT1 NM_001478.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 0.629

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:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 12-57625419-C-T is Benign according to our data. Variant chr12-57625419-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1686497.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00239 (364/152260) while in subpopulation AMR AF= 0.00608 (93/15302). AF 95% confidence interval is 0.00508. There are 2 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALNT1	NM_001478.5	c.*1325G>A		3_prime_UTR_variant	11/11	ENST00000341156.9	NP_001469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156	c.*1325G>A		3_prime_UTR_variant	11/11	1	NM_001478.5	ENSP00000341562.4
ENSG00000287908	ENST00000474359.7	n.*1689C>T		non_coding_transcript_exon_variant	21/23	5		ENSP00000431994.2
ENSG00000287908	ENST00000474359.7	n.*1689C>T		3_prime_UTR_variant	21/23	5		ENSP00000431994.2

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152142 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00326

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00237 AC: 597 AN: 251456 Hom.: 5 AF XY: 0.00255 AC XY: 347 AN XY: 135900

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00573

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000686

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00309

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00270 AC: 3941 AN: 1461876 Hom.: 13 Cov.: 38 AF XY: 0.00266 AC XY: 1935 AN XY: 727244

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00597

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000707

Gnomad4 FIN exome AF: 0.000243

Gnomad4 NFE exome AF: 0.00304

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152260 Hom.: 2 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74440

Gnomad4 AFR AF: 0.000650

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00326

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00187 Hom.: 1

Bravo AF: 0.00261

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00326 AC: 28

ExAC AF: 0.00227 AC: 275

EpiCase AF: 0.00403

EpiControl AF: 0.00451

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	SLC26A10P: BS2 -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Pathogenic	0.29
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.0046
FATHMM_MKL	Benign	0.13	N
Vest4		0.078
GERP RS		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs151077423; hg19: chr12-58019202;