10-79556699-C-A

Position:

• chr10-79556699-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098668.4(SFTPA2):​c.*510G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 150,714 control chromosomes in the GnomAD database, including 10,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (10750 hom., cov: 33)
  • Exomes 𝑓: 0.33 (2237 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFTPA2 NM_001098668.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

SFTPA2 (HGNC:10799): (surfactant protein A2) This gene is one of several genes encoding pulmonary-surfactant associated proteins (SFTPA) located on chromosome 10. Mutations in this gene and a highly similar gene located nearby, which affect the highly conserved carbohydrate recognition domain, are associated with idiopathic pulmonary fibrosis. The current version of the assembly displays only a single centromeric SFTPA gene pair rather than the two gene pairs shown in the previous assembly which were thought to have resulted from a duplication. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA2	NM_001098668.4	c.*510G>T		3_prime_UTR_variant	6/6	ENST00000372325.7	NP_001092138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7	c.*510G>T		3_prime_UTR_variant	6/6	1	NM_001098668.4	ENSP00000361400.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58170 AN: 150598 Hom.: 10700 Cov.: 33

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.403

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.334 AC: 11732 AN: 35100 Hom.: 2237 Cov.: 0 AF XY: 0.347 AC XY: 6174 AN XY: 17768

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.387 AC: 58286 AN: 150714 Hom.: 10750 Cov.: 33 AF XY: 0.391 AC XY: 28775 AN XY: 73676

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.409

Alfa AF: 0.396 Hom.: 1315

Bravo AF: 0.401

Asia WGS AF: 0.527 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs17879335; hg19: chr10-81316455;