NM_005411.5:c.186A>G

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.186A>G(p.Pro62Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,446 control chromosomes in the GnomAD database, including 24,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2661 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21977 hom. )

Consequence

SFTPA1
NM_005411.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.93

Publications

34 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=-0.7).

BP6

Variant 10-79612325-A-G is Benign according to our data. Variant chr10-79612325-A-G is described in ClinVar as [Benign]. Clinvar id is 165197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5 link	c.186A>G	p.Pro62Pro	synonymous_variant	Exon 4 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.186A>G	p.Pro62Pro	synonymous_variant	Exon 4 of 6	1	NM_005411.5	ENSP00000381633.3	Q8IWL2-1
SFTPA1	ENST00000419470.6 link	c.231A>G	p.Pro77Pro	synonymous_variant	Exon 4 of 6	1		ENSP00000397082.2	Q8IWL2-2
SFTPA1	ENST00000428376.6 link	c.186A>G	p.Pro62Pro	synonymous_variant	Exon 3 of 5	1		ENSP00000411102.2	Q8IWL2-1
SFTPA1	ENST00000429958.5 link	c.186A>G	p.Pro62Pro	synonymous_variant	Exon 3 of 5	1		ENSP00000395527.1	A0A0C4DG36

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27012

AN:

151896

Hom.:

2651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.212

GnomAD2 exomes

AF:

0.206

AC:

51721

AN:

251438

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.167

AC:

244707

AN:

1461434

Hom.:

21977

Cov.:

AF XY:

0.169

AC XY:

123216

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.157

AC:

5242

AN:

33474

American (AMR)

AF:

0.327

AC:

14626

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

5714

AN:

26120

East Asian (EAS)

AF:

0.246

AC:

9779

AN:

39672

South Asian (SAS)

AF:

0.252

AC:

21736

AN:

86248

European-Finnish (FIN)

AF:

0.159

AC:

8510

AN:

53362

Middle Eastern (MID)

AF:

0.225

AC:

1293

AN:

5756

European-Non Finnish (NFE)

AF:

0.150

AC:

166698

AN:

1111728

Other (OTH)

AF:

0.184

AC:

11109

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

11414

22828

34243

45657

57071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.178

AC:

27062

AN:

152012

Hom.:

2661

Cov.:

AF XY:

0.183

AC XY:

13619

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.158

AC:

6568

AN:

41462

American (AMR)

AF:

0.285

AC:

4361

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

783

AN:

3466

East Asian (EAS)

AF:

0.257

AC:

1323

AN:

5148

South Asian (SAS)

AF:

0.276

AC:

1330

AN:

4816

European-Finnish (FIN)

AF:

0.144

AC:

1522

AN:

10582

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10537

AN:

67946

Other (OTH)

AF:

0.218

AC:

459

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1121

2243

3364

4486

5607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.143

Hom.:

740

Bravo

AF:

0.187

Asia WGS

AF:

0.289

AC:

1003

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 13, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Benign based on MAF in ESP (16.7% in AA; 15.82% in EA) -

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

-0.70

CADD

Benign

0.43

(source)

DANN

Benign

0.40

PhyloP100

-2.9

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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NM_005411.5:c.186A>G

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