chr12-57625419-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

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

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.629

Variant links:

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]

B4GALNT1 links:

ENSG00000287908 (HGNC:):

ENSG00000287908 links:

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]

SLC26A10P links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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: {Uncertain_significance=2, Likely_benign=1}.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT1	NM_001478.5 link	c.*1325G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341156.9	NP_001469.1	Q00973-1B4DSP5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
B4GALNT1	ENST00000341156 link	c.*1325G>A	3_prime_UTR_variant	Exon 11 of 11	1	NM_001478.5	ENSP00000341562.4	Q00973-1
ENSG00000287908	ENST00000474359.7 link	n.*1689C>T	non_coding_transcript_exon_variant	Exon 21 of 23	5		ENSP00000431994.2	E9PIH7
ENSG00000287908	ENST00000474359.7 link	n.*1689C>T	3_prime_UTR_variant	Exon 21 of 23	5		ENSP00000431994.2	E9PIH7

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152142

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00237

AC:

597

AN:

251456

AF XY:

0.00255

show subpopulations

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 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.:

Cov.:

AF XY:

0.00266

AC XY:

1935

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00597

AC:

267

AN:

44720

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26134

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.000707

AC:

AN:

86254

Gnomad4 FIN exome

AF:

0.000243

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.00304

AC:

3386

AN:

1112004

Gnomad4 Remaining exome

AF:

0.00310

AC:

187

AN:

60396

Heterozygous variant carriers

267

534

802

1069

1336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152260

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000650

AC:

0.000649882

AN:

0.000649882

Gnomad4 AMR

AF:

0.00608

AC:

0.00607764

AN:

0.00607764

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000193

AC:

0.000193199

AN:

0.000193199

Gnomad4 SAS

AF:

0.000622

AC:

0.000621891

AN:

0.000621891

Gnomad4 FIN

AF:

0.000377

AC:

0.000377145

AN:

0.000377145

Gnomad4 NFE

AF:

0.00326

AC:

0.00326375

AN:

0.00326375

Gnomad4 OTH

AF:

0.00379

AC:

0.00378788

AN:

0.00378788

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00261

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00227

AC:

275

EpiCase

AF:

0.00403

EpiControl

AF:

0.00451

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC26A10P: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Uncertain:1

May 04, 2022

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Pathogenic

0.29

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.0046

FATHMM_MKL

Benign

0.13

Vest4

0.078

GERP RS

2.2

Mutation Taster

=188/12

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over