Variant 11-62423081-T-C 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_003357.5(SCGB1A1):c.266T>C(p.Leu89Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCGB1A1
NM_003357.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.87

Variant links:

Genes affected

SCGB1A1 (HGNC:12523): (secretoglobin family 1A member 1) This gene encodes a member of the secretoglobin family of small secreted proteins. The encoded protein has been implicated in numerous functions including anti-inflammation, inhibition of phospholipase A2 and the sequestering of hydrophobic ligands. Defects in this gene are associated with a susceptibility to asthma. [provided by RefSeq, May 2010]

SCGB1A1 links:

(HGNC:):

links:

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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=0.20850551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCGB1A1	NM_003357.5 linkuse as main transcript	c.266T>C	p.Leu89Pro	missense_variant	3/3	ENST00000278282.3
LOC102723765	XR_007062699.1 linkuse as main transcript	n.237+3606A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCGB1A1	ENST00000278282.3 linkuse as main transcript	c.266T>C	p.Leu89Pro	missense_variant	3/3	1	NM_003357.5	P1
	ENST00000528983.1 linkuse as main transcript	n.39-765A>G		intron_variant, non_coding_transcript_variant		3
SCGB1A1	ENST00000534397.5 linkuse as main transcript	c.161T>C	p.Leu54Pro	missense_variant	4/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 30, 2023

The c.266T>C (p.L89P) alteration is located in exon 3 (coding exon 3) of the SCGB1A1 gene. This alteration results from a T to C substitution at nucleotide position 266, causing the leucine (L) at amino acid position 89 to be replaced by a proline (P). 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

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.23

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.80

N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.5

D;N

REVEL

Benign

0.089

Sift

Benign

0.045

D;T

Sift4G

Uncertain

0.049

D;T

Polyphen

0.98

.;D

Vest4

0.078

MutPred

0.71

.;Loss of stability (P = 0.0213);

MVP

0.22

MPC

0.70

ClinPred

0.39

GERP RS

-2.7

Varity_R

0.15

gMVP

0.32

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

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