rs41265203

Variant names:

• chr1-193181196-A-C
• rs41265203
• NM_003783.3:c.367T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-193181196-A-C
• chr1-193181196-A-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003783.3(B3GALT2):​c.367T>G​(p.Tyr123Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00238 in 1,613,784 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (5 hom.)
• Consequence: B3GALT2 NM_003783.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.96
• Publications: 7 publications found

Genes affected

B3GALT2 (HGNC:917): (beta-1,3-galactosyltransferase 2) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). This gene encodes a protein that functions in N-linked glycoprotein glycosylation and shows strict donor substrate specificity for UDP-galactose. [provided by RefSeq, Jul 2008]

CDC73 (HGNC:16783): (cell division cycle 73) This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]

CDC73 Gene-Disease associations (from GenCC):

• hyperparathyroidism 2 with jaw tumors

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
• hyperparathyroidism 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• parathyroid gland carcinoma

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated hyperparathyroidism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308280 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008090198).
• BP6: Variant 1-193181196-A-C is Benign according to our data. Variant chr1-193181196-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 226036.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003783.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT2	NM_003783.3	MANE Select	c.367T>G	p.Tyr123Asp	missense	Exon 2 of 2	NP_003774.1	O43825
	CDC73	NM_024529.5	MANE Select	c.973-22599A>C		intron	N/A	NP_078805.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT2	ENST00000367434.5	TSL:1 MANE Select	c.367T>G	p.Tyr123Asp	missense	Exon 2 of 2	ENSP00000356404.4	O43825
	CDC73	ENST00000367435.5	TSL:1 MANE Select	c.973-22599A>C		intron	N/A	ENSP00000356405.4	Q6P1J9
	B3GALT2	ENST00000958440.1		c.367T>G	p.Tyr123Asp	missense	Exon 2 of 2	ENSP00000628499.1

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152110 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00123 AC: 308 AN: 251150 AF XY: 0.00124

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00208

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00244 AC: 3563 AN: 1461556 Hom.: 5 Cov.: 32 AF XY: 0.00240 AC XY: 1742 AN XY: 727090

African (AFR) AF: 0.000479 AC: 16 AN: 33434

American (AMR) AF: 0.00163 AC: 73 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86218

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00298 AC: 3316 AN: 1111888

Other (OTH) AF: 0.00239 AC: 144 AN: 60370

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152228 Hom.: 1 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74434

African (AFR) AF: 0.000457 AC: 19 AN: 41554

American (AMR) AF: 0.00432 AC: 66 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 67986

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00229 Hom.: 0

Bravo AF: 0.00198

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.000997 AC: 121

EpiCase AF: 0.00224

EpiControl AF: 0.00219

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hyperparathyroidism 2 with jaw tumors (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		5.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.078
Sift	Benign	0.096	T
Sift4G	Benign	0.23	T
Polyphen		0.0080	B
Vest4		0.45
MVP		0.46
MPC		0.76
ClinPred		0.012	T
GERP RS		5.3
Varity_R		0.20
gMVP		0.68
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs41265203; hg19: chr1-193150326; COSMIC: COSV108198877;