8-22162553-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001317778.2(SFTPC):c.43-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,611,794 control chromosomes in the GnomAD database, including 169,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20258 hom., cov: 32)
  • Exomes 𝑓: 0.45 (148919 hom.)
• Consequence: SFTPC NM_001317778.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-22162553-T-C is Benign according to our data. Variant chr8-22162553-T-C is described in ClinVar as [Benign]. Clinvar id is 1272642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPC	NM_001317778.2	c.43-21T>C		intron_variant		ENST00000679463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPC	ENST00000679463.1	c.43-21T>C		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76426 AN: 151966 Hom.: 20223 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.504

GnomAD3 exomes AF: 0.494 AC: 122960 AN: 248714 Hom.: 32051 AF XY: 0.488 AC XY: 65930 AN XY: 134996

Gnomad AFR exome AF: 0.637

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.795

Gnomad SAS exome AF: 0.503

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.473

GnomAD4 exome AF: 0.446 AC: 650445 AN: 1459706 Hom.: 148919 Cov.: 40 AF XY: 0.446 AC XY: 324107 AN XY: 726238

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.747

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.503 AC: 76521 AN: 152088 Hom.: 20258 Cov.: 32 AF XY: 0.505 AC XY: 37504 AN XY: 74334

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.507

Alfa AF: 0.467 Hom.: 4849

Bravo AF: 0.522

Asia WGS AF: 0.615 AC: 2137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Surfactant metabolism dysfunction, pulmonary, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.0
Dann	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs13248346; hg19: chr8-22020066; COSMIC: COSV59345905; COSMIC: COSV59345905;