rs1059057

Variant names:

• chr10-79613765-A-G
• rs1059057
• NM_005411.5:c.399A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.33
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• interstitial lung disease 1

  Inheritance: AD, SD Classification: STRONG, MODERATE Submitted by: ClinGen, PanelApp Australia

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005411.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA1	NM_005411.5	MANE Select	c.399A>G	p.Thr133Thr	synonymous	Exon 6 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.444A>G	p.Thr148Thr	synonymous	Exon 6 of 6	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.399A>G	p.Thr133Thr	synonymous	Exon 6 of 6	NP_001158116.1	Q8IWL2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA1	ENST00000398636.8	TSL:1 MANE Select	c.399A>G	p.Thr133Thr	synonymous	Exon 6 of 6	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.444A>G	p.Thr148Thr	synonymous	Exon 6 of 6	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.399A>G	p.Thr133Thr	synonymous	Exon 5 of 5	ENSP00000411102.2	Q8IWL2-1

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

GnomAD2 exomes AF: 0.0988 AC: 24723 AN: 250160 AF XY: 0.0995

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

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

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

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: 87 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: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4588 AN: 68018

Other (OTH) AF: 0.0872 AC: 184 AN: 2110

Alfa AF: 0.0707 Hom.: 86

Bravo AF: 0.0716

EpiCase AF: 0.0711

EpiControl AF: 0.0666

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	SFTPA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.33
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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