12-57625419-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]

(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 -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
SLC26A10P	NR_166679.1	n.2272C>T		non_coding_transcript_exon_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.*1325G>A		3_prime_UTR_variant	11/11	1	NM_001478.5	ENSP00000341562	P1
	ENST00000440686.5	n.1450C>T		non_coding_transcript_exon_variant	14/16	2
SLC26A10P	ENST00000665594.1	n.1879C>T		non_coding_transcript_exon_variant	16/18

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

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

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
MutationTaster	Benign	1.0	D;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;