rs1059057

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005411.5(SFTPA1):c.399A>G(p.Thr133Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,613,874 control chromosomes in the GnomAD database, including 6,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 552 hom., cov: 32)

Exomes 𝑓: 0.077 ( 5723 hom. )

Consequence

SFTPA1
NM_005411.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.33

Publications

19 publications found

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 10-79613765-A-G is Benign according to our data. Variant chr10-79613765-A-G is described in ClinVar as Benign. ClinVar VariationId is 165199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5 link	c.399A>G	p.Thr133Thr	synonymous_variant	Exon 6 of 6	ENST00000398636.8	NP_005402.3	Q8IWL2-1A0A024QZP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFTPA1	ENST00000398636.8 link	c.399A>G	p.Thr133Thr	synonymous_variant	Exon 6 of 6	1	NM_005411.5	ENSP00000381633.3	Q8IWL2-1
SFTPA1	ENST00000419470.6 link	c.444A>G	p.Thr148Thr	synonymous_variant	Exon 6 of 6	1		ENSP00000397082.2	Q8IWL2-2
SFTPA1	ENST00000428376.6 link	c.399A>G	p.Thr133Thr	synonymous_variant	Exon 5 of 5	1		ENSP00000411102.2	Q8IWL2-1
SFTPA1	ENST00000429958.5 link	c.399A>G	p.Thr133Thr	synonymous_variant	Exon 5 of 5	1		ENSP00000395527.1	A0A0C4DG36

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

10071

AN:

152128

Hom.:

545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0209

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.0783

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.0454

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0674

Gnomad OTH

AF:

0.0833

GnomAD2 exomes

AF:

0.0988

AC:

24723

AN:

250160

AF XY:

0.0995

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.0748

Gnomad EAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0527

Gnomad NFE exome

AF:

0.0675

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0768

AC:

112221

AN:

1461628

Hom.:

5723

Cov.:

AF XY:

0.0796

AC XY:

57904

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.0180

AC:

603

AN:

33470

American (AMR)

AF:

0.233

AC:

10401

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0754

AC:

1969

AN:

26130

East Asian (EAS)

AF:

0.0220

AC:

873

AN:

39700

South Asian (SAS)

AF:

0.187

AC:

16142

AN:

86244

European-Finnish (FIN)

AF:

0.0517

AC:

2763

AN:

53418

Middle Eastern (MID)

AF:

0.107

AC:

618

AN:

5758

European-Non Finnish (NFE)

AF:

0.0667

AC:

74190

AN:

1111814

Other (OTH)

AF:

0.0772

AC:

4662

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

6535

13070

19606

26141

32676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2916

5832

8748

11664

14580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0663

AC:

10090

AN:

152246

Hom.:

552

Cov.:

AF XY:

0.0698

AC XY:

5197

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0208

AC:

865

AN:

41564

American (AMR)

AF:

0.171

AC:

2621

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0783

AC:

272

AN:

3472

East Asian (EAS)

AF:

0.0168

AC:

AN:

5166

South Asian (SAS)

AF:

0.200

AC:

961

AN:

4800

European-Finnish (FIN)

AF:

0.0454

AC:

482

AN:

10610

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0675

AC:

4588

AN:

68018

Other (OTH)

AF:

0.0872

AC:

184

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

457

915

1372

1830

2287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0707

Hom.:

Bravo

AF:

0.0716

EpiCase

AF:

0.0711

EpiControl

AF:

0.0666

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Thr148Thr in exon 6 of SFTPA1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 6.7% (572/8586) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs141764116). -

SFTPA1-related disorder

Benign:1

Apr 22, 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). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.42

(source)

DANN

Benign

0.33

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over