rs1059057

chr10-79613765-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005411.5(SFTPA1):c.399A>G(p.Thr133=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33

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 Benign. Variant got -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 id 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/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.399A>G	p.Thr133=	synonymous_variant	6/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.399A>G	p.Thr133=	synonymous_variant	6/6	1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.444A>G	p.Thr148=	synonymous_variant	6/6	1
SFTPA1	ENST00000428376.6	c.399A>G	p.Thr133=	synonymous_variant	5/5	1		P1
SFTPA1	ENST00000429958.5	c.399A>G	p.Thr133=	synonymous_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10071 AN: 152128 Hom.: 545 Cov.: 32

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

GnomAD3 exomes AF: 0.0988 AC: 24723 AN: 250160 Hom.: 2024 AF XY: 0.0995 AC XY: 13472 AN XY: 135440

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 SAS exome AF: 0.187

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.: 32 AF XY: 0.0796 AC XY: 57904 AN XY: 727116

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0667

Gnomad4 OTH exome AF: 0.0772

GnomAD4 genome AF: 0.0663 AC: 10090 AN: 152246 Hom.: 552 Cov.: 32 AF XY: 0.0698 AC XY: 5197 AN XY: 74432

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.0783

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0454

Gnomad4 NFE AF: 0.0675

Gnomad4 OTH AF: 0.0872

Alfa AF: 0.0707 Hom.: 86

Bravo AF: 0.0716

EpiCase AF: 0.0711

EpiControl AF: 0.0666

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 27, 2019

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	-0.96
Cadd	Benign	0.42
Dann	Benign	0.33

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: rs1059057; hg19: chr10-81373521; COSMIC: COSV64866748; COSMIC: COSV64866748;