Variant 12-48569177-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002289.3(LALBA):c.197G>A(p.Ser66Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,613,574 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

LALBA
NM_002289.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.414

Variant links:

Genes affected

LALBA (HGNC:6480): (lactalbumin alpha) This gene encodes alpha-lactalbumin, a principal protein of milk. Alpha-lactalbumin forms the regulatory subunit of the lactose synthase (LS) heterodimer and beta 1,4-galactosyltransferase (beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce lactose by transfering galactose moieties to glucose. As a monomer, alpha-lactalbumin strongly binds calcium and zinc ions and may possess bactericidal or antitumor activity. A folding variant of alpha-lactalbumin, called HAMLET, likely induces apoptosis in tumor and immature cells. [provided by RefSeq, Jul 2008]

LALBA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10741967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LALBA	NM_002289.3 link	c.197G>A	p.Ser66Asn	missense_variant	2/4	ENST00000301046.6	NP_002280.1	P00709A0A080YV01
LALBA	NM_001384350.1 link	c.197G>A	p.Ser66Asn	missense_variant	3/5		NP_001371279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LALBA	ENST00000301046.6 link	c.197G>A	p.Ser66Asn	missense_variant	2/4	1	NM_002289.3	ENSP00000301046.2		P00709
LALBA	ENST00000549817.1 link	c.197G>A	p.Ser66Asn	missense_variant	2/3	5		ENSP00000449780.1		F8VWU1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000135

AC:

AN:

251108

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000185

AC:

270

AN:

1461306

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000105

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000199

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.197G>A (p.S66N) alteration is located in exon 2 (coding exon 2) of the LALBA gene. This alteration results from a G to A substitution at nucleotide position 197, causing the serine (S) at amino acid position 66 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.7

DANN

Benign

0.93

DEOGEN2

Uncertain

0.55

D;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.14

Sift

Benign

0.075

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0

B;.

Vest4

0.068

MVP

0.69

MPC

0.44

ClinPred

0.041

GERP RS

1.1

Varity_R

0.35

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over