dbSNP rs3997775: SFTPA1:c.-23-5T>A (chr10-79611798-T-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_005411.5(SFTPA1):c.-23-5T>A variant causes a splice region, 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. Variant has been reported in ClinVar as Benign (no stars).

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, intron

Scores

Splicing: ADA: 0.9993

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.30

Variant links:

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]

SFTPA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP6

Variant 10-79611798-T-A is Benign according to our data. Variant chr10-79611798-T-A is described in ClinVar as [Benign]. Clinvar id is 3355976.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5 link	c.-23-5T>A		splice_region_variant, intron_variant	Intron 2 of 5	ENST00000398636.8	NP_005402.3	Q8IWL2-1A0A024QZP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8 link	c.-23-5T>A		splice_region_variant, intron_variant	Intron 2 of 5	1	NM_005411.5	ENSP00000381633.3		Q8IWL2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1596

AN:

107188

Hom.:

Cov.:

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.:

Cov.:

105

AF XY:

0.197

AC XY:

86314

AN XY:

439148

show subpopulations

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.:

Cov.:

AF XY:

0.0160

AC XY:

838

AN XY:

52510

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SFTPA1-related disorder

Benign:1

Sep 25, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

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

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