NM_001317778.2:c.43-194G>A

Variant names:

• chr8-22162380-G-A
• rs8192325
• NM_001317778.2:c.43-194G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001317778.2(SFTPC):​c.43-194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,066 control chromosomes in the GnomAD database, including 5,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5726 hom., cov: 32)
• Consequence: SFTPC NM_001317778.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268
• Publications: 1 publications found

Genes affected

SFTPC (HGNC:10802): (surfactant protein C) This gene encodes the pulmonary-associated surfactant protein C (SPC), an extremely hydrophobic surfactant protein essential for lung function and homeostasis after birth. Pulmonary surfactant is a surface-active lipoprotein complex composed of 90% lipids and 10% proteins which include plasma proteins and apolipoproteins SPA, SPB, SPC and SPD. The surfactant is secreted by the alveolar cells of the lung and maintains the stability of pulmonary tissue by reducing the surface tension of fluids that coat the lung. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 2, also called pulmonary alveolar proteinosis due to surfactant protein C deficiency, and are associated with interstitial lung disease in older infants, children, and adults. Alternatively spliced transcript variants encoding different protein isoforms have been identified.[provided by RefSeq, Feb 2010]

SFTPC Gene-Disease associations (from GenCC):

• SFTPC-related interstitial lung disease

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• surfactant metabolism dysfunction, pulmonary, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• chronic respiratory distress with surfactant metabolism deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-22162380-G-A is Benign according to our data. Variant chr8-22162380-G-A is described in ClinVar as Benign. ClinVar VariationId is 1244660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317778.2. 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
	SFTPC	NM_001317778.2	MANE Select	c.43-194G>A		intron	N/A	NP_001304707.1	P11686-2
	SFTPC	NM_001172410.2		c.43-194G>A		intron	N/A	NP_001165881.1	A0A0S2Z4Q0
	SFTPC	NM_001385653.1		c.43-194G>A		intron	N/A	NP_001372582.1	P11686-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPC	ENST00000679463.1	MANE Select	c.43-194G>A		intron	N/A	ENSP00000505152.1	P11686-2
	SFTPC	ENST00000318561.7	TSL:1	c.43-194G>A		intron	N/A	ENSP00000316152.3	P11686-1
	SFTPC	ENST00000521315.5	TSL:1	c.43-194G>A		intron	N/A	ENSP00000430410.1	P11686-2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40742 AN: 151948 Hom.: 5726 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.268 AC: 40755 AN: 152066 Hom.: 5726 Cov.: 32 AF XY: 0.262 AC XY: 19473 AN XY: 74328

African (AFR) AF: 0.323 AC: 13383 AN: 41452

American (AMR) AF: 0.238 AC: 3642 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3470

East Asian (EAS) AF: 0.176 AC: 908 AN: 5172

South Asian (SAS) AF: 0.165 AC: 796 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2336 AN: 10594

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17704 AN: 67970

Other (OTH) AF: 0.283 AC: 596 AN: 2106

Alfa AF: 0.259 Hom.: 7968

Bravo AF: 0.273

Asia WGS AF: 0.193 AC: 674 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8192325; hg19: chr8-22019893;