12-57624077-G-A

Position:

• chr12-57624077-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP3_Moderate BP6 BS1 BS2

The NM_001478.5(B4GALNT1):​c.*2667C>T variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,613,852 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (27 hom.)
• Consequence: B4GALNT1 NM_001478.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 8.41

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 -7 ACMG points.

• PP3: BayesDel_addAF computational evidence supports a deleterious effect, 0.234
• BP6: Variant 12-57624077-G-A is Benign according to our data. Variant chr12-57624077-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1686495.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00394 (600/152218) while in subpopulation NFE AF= 0.00595 (405/68016). AF 95% confidence interval is 0.00548. There are 0 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALNT1	NM_001478.5	c.*2667C>T		3_prime_UTR_variant	11/11	ENST00000341156.9	NP_001469.1
SLC26A10P	NR_166679.1	n.1900G>A		non_coding_transcript_exon_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.*2667C>T		3_prime_UTR_variant	11/11	1	NM_001478.5	ENSP00000341562	P1
	ENST00000440686.5	n.1078G>A		non_coding_transcript_exon_variant	9/16	2
SLC26A10P	ENST00000665594.1	n.1437G>A		non_coding_transcript_exon_variant	10/18

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 601 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00595

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00399 AC: 1001 AN: 251120 Hom.: 6 AF XY: 0.00406 AC XY: 551 AN XY: 135700

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00408

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00236

Gnomad FIN exome AF: 0.00268

Gnomad NFE exome AF: 0.00609

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00531 AC: 7764 AN: 1461634 Hom.: 27 Cov.: 33 AF XY: 0.00520 AC XY: 3781 AN XY: 727104

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.00318

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00244

Gnomad4 FIN exome AF: 0.00292

Gnomad4 NFE exome AF: 0.00612

Gnomad4 OTH exome AF: 0.00517

GnomAD4 genome AF: 0.00394 AC: 600 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.00372 AC XY: 277 AN XY: 74438

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00595

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00555 Hom.: 5

Bravo AF: 0.00400

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00558 AC: 48

ExAC AF: 0.00418 AC: 507

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00736

EpiControl AF: 0.00605

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

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
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Pathogenic	0.57
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.97	D
MutationTaster	Benign	1.0	A;A
Vest4		0.40
GERP RS		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs113207856; hg19: chr12-58017860; COSMIC: COSV57541420; COSMIC: COSV57541420;