rs3997775

chr10-79611798-T-Achr10-79611798-T-Cchr10-79611798-T-G

Variant summary

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

The NM_005411.5(SFTPA1):c.-23-5T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.21 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFTPA1 NM_005411.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.9993
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.-23-5T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.-23-5T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005411.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1596 AN: 107188 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00899

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00418

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.00981

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0176

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.206 AC: 181168 AN: 877824 Hom.: 5 Cov.: 105 AF XY: 0.197 AC XY: 86314 AN XY: 439148

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.0670

Gnomad4 ASJ exome AF: 0.0569

Gnomad4 EAS exome AF: 0.0690

Gnomad4 SAS exome AF: 0.0582

Gnomad4 FIN exome AF: 0.0396

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0149 AC: 1594 AN: 107304 Hom.: 0 Cov.: 33 AF XY: 0.0160 AC XY: 838 AN XY: 52510

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.00418

Gnomad4 EAS AF: 0.0257

Gnomad4 SAS AF: 0.00981

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0173

Alfa AF: 0.0874 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	16
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.91
SpliceAI score (max)		0.65		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.65		Position offset: 2
DS_AL_spliceai		0.31		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3997775; hg19: chr10-81371554; COSMIC: COSV64866565;