rs1059058

Variant names:

• chr10-79613972-C-T
• rs1059058
• NM_005411.5:c.606C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005411.5(SFTPA1):​c.606C>T​(p.Asp202Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,610,506 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (44 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (45 hom.)
• Consequence: SFTPA1 NM_005411.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0960
• Publications: 3 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 Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-79613972-C-T is Benign according to our data. Variant chr10-79613972-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.096 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (2180/151926) while in subpopulation AFR AF = 0.0494 (2045/41392). AF 95% confidence interval is 0.0476. There are 44 homozygotes in GnomAd4. There are 1009 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AD,AR gene

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.606C>T	p.Asp202Asp	synonymous	Exon 6 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.651C>T	p.Asp217Asp	synonymous	Exon 6 of 6	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.606C>T	p.Asp202Asp	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.606C>T	p.Asp202Asp	synonymous	Exon 6 of 6	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.651C>T	p.Asp217Asp	synonymous	Exon 6 of 6	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.606C>T	p.Asp202Asp	synonymous	Exon 5 of 5	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2173 AN: 151810 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00137 AC: 343 AN: 250714 AF XY: 0.00116

Gnomad AFR exome AF: 0.0186

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.000788 AC: 1149 AN: 1458580 Hom.: 45 Cov.: 33 AF XY: 0.000761 AC XY: 552 AN XY: 725832

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0226 AC: 718 AN: 31812

American (AMR) AF: 0.00119 AC: 53 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.000454 AC: 18 AN: 39678

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86230

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53412

Middle Eastern (MID) AF: 0.000870 AC: 5 AN: 5748

European-Non Finnish (NFE) AF: 0.000201 AC: 223 AN: 1110718

Other (OTH) AF: 0.00173 AC: 104 AN: 60228

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0143 AC: 2180 AN: 151926 Hom.: 44 Cov.: 32 AF XY: 0.0136 AC XY: 1009 AN XY: 74244

African (AFR) AF: 0.0494 AC: 2045 AN: 41392

American (AMR) AF: 0.00510 AC: 78 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000776 AC: 4 AN: 5154

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 67932

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00728 Hom.: 4

Bravo AF: 0.0157

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism

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: rs1059058; hg19: chr10-81373728;