12-57624885-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]

(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 -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	UniProt
B4GALNT1	NM_001478.5	c.*1859A>C		3_prime_UTR_variant	11/11	ENST00000341156.9
SLC26A10P	NR_166679.1	n.2048T>G		non_coding_transcript_exon_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.*1859A>C		3_prime_UTR_variant	11/11	1	NM_001478.5	P1
	ENST00000440686.5	n.1226T>G		non_coding_transcript_exon_variant	11/16	2
SLC26A10P	ENST00000665594.1	n.1655T>G		non_coding_transcript_exon_variant	13/18

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

Nov 01, 2022

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
MutationTaster	Benign	0.57	N;N
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;