11-62423081-T-C

Position:

• chr11-62423081-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.87

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]

ENSG00000255446 (HGNC:):

ACMG classification

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	Protein	UniProt
SCGB1A1	NM_003357.5	c.266T>C	p.Leu89Pro	missense_variant	3/3	ENST00000278282.3	NP_003348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCGB1A1	ENST00000278282.3	c.266T>C	p.Leu89Pro	missense_variant	3/3	1	NM_003357.5	ENSP00000278282.2
SCGB1A1	ENST00000534397.5	c.161T>C	p.Leu54Pro	missense_variant	4/4	3		ENSP00000432866.1
ENSG00000255446	ENST00000528983.1	n.39-765A>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
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	N
LIST_S2	Benign	0.25	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.27	T
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	T
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

Other links and lift over

dbSNP: rs1937842519; hg19: chr11-62190553;