10-79613943-CCC-TCT

Variant names:

• chr10-79613943-CCC-TCT
• NM_005411.5:c.577_579delCCCinsTCT
• SFTPA1 p.Pro193Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005411.5(SFTPA1):​c.577_579delCCCinsTCT​(p.Pro193Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.577_579delCCCinsTCT	p.Pro193Ser	missense	N/A	NP_005402.3
	SFTPA1	NM_001093770.3		c.622_624delCCCinsTCT	p.Pro208Ser	missense	N/A	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.577_579delCCCinsTCT	p.Pro193Ser	missense	N/A	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.577_579delCCCinsTCT	p.Pro193Ser	missense	N/A	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.622_624delCCCinsTCT	p.Pro208Ser	missense	N/A	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.577_579delCCCinsTCT	p.Pro193Ser	missense	N/A	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.075

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-81373699;