chr12-57624885-T-G

Position:

• chr12-57624885-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001478.5(B4GALNT1):​c.*1859A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00607 in 1,614,102 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (34 hom.)
• Consequence: B4GALNT1 NM_001478.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045810133).
• BP6: Variant 12-57624885-T-G is Benign according to our data. Variant chr12-57624885-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00589 (897/152238) while in subpopulation AMR AF= 0.00837 (128/15300). AF 95% confidence interval is 0.00719. There are 2 homozygotes in gnomad4. There are 421 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.*1859A>C		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.*1859A>C		3_prime_UTR_variant	11/11	1	NM_001478.5	ENSP00000341562.4
ENSG00000287908	ENST00000474359.7	n.*1465T>G		non_coding_transcript_exon_variant	18/23	5		ENSP00000431994.2
ENSG00000287908	ENST00000474359.7	n.*1465T>G		3_prime_UTR_variant	18/23	5		ENSP00000431994.2

Frequencies

GnomAD3 genomes AF: 0.00590 AC: 898 AN: 152120 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00469

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00701

Gnomad OTH AF: 0.00815

GnomAD3 exomes AF: 0.00522 AC: 1312 AN: 251444 Hom.: 10 AF XY: 0.00530 AC XY: 720 AN XY: 135888

Gnomad AFR exome AF: 0.00431

Gnomad AMR exome AF: 0.00520

Gnomad ASJ exome AF: 0.00486

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00261

Gnomad FIN exome AF: 0.00268

Gnomad NFE exome AF: 0.00730

Gnomad OTH exome AF: 0.00734

GnomAD4 exome AF: 0.00608 AC: 8893 AN: 1461864 Hom.: 34 Cov.: 32 AF XY: 0.00601 AC XY: 4370 AN XY: 727236

Gnomad4 AFR exome AF: 0.00385

Gnomad4 AMR exome AF: 0.00626

Gnomad4 ASJ exome AF: 0.00436

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00261

Gnomad4 FIN exome AF: 0.00294

Gnomad4 NFE exome AF: 0.00675

Gnomad4 OTH exome AF: 0.00685

GnomAD4 genome AF: 0.00589 AC: 897 AN: 152238 Hom.: 2 Cov.: 32 AF XY: 0.00565 AC XY: 421 AN XY: 74454

Gnomad4 AFR AF: 0.00467

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00701

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00600 Hom.: 7

Bravo AF: 0.00629

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.00409 AC: 18

ESP6500EA AF: 0.00686 AC: 59

ExAC AF: 0.00537 AC: 652

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00889

EpiControl AF: 0.00806

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

SLC26A10P: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	0.030
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.046	T
MetaSVM	Uncertain	0.39	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.87
MVP		0.70
MPC		0.74
ClinPred		0.023	T
GERP RS		3.6
Varity_R		0.63
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs111924104; hg19: chr12-58018668; COSMIC: COSV57545301; COSMIC: COSV57545301;