rs1059056

Positions:

• chr10-79613238-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005411.5(SFTPA1):​c.342T>C​(p.Phe114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 151,880 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (26 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFTPA1 NM_005411.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00900

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-79613238-T-C is Benign according to our data. Variant chr10-79613238-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 227063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.009 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00363 (551/151880) while in subpopulation EAS AF= 0.025 (128/5120). AF 95% confidence interval is 0.0215. There are 4 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.342T>C	p.Phe114=	synonymous_variant	5/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.342T>C	p.Phe114=	synonymous_variant	5/6	1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.387T>C	p.Phe129=	synonymous_variant	5/6	1
SFTPA1	ENST00000428376.6	c.342T>C	p.Phe114=	synonymous_variant	4/5	1		P1
SFTPA1	ENST00000429958.5	c.342T>C	p.Phe114=	synonymous_variant	4/5	1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 550 AN: 151762 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0255

Gnomad SAS AF: 0.00728

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.000810

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00287 AC: 721 AN: 250964 Hom.: 8 AF XY: 0.00291 AC XY: 395 AN XY: 135634

Gnomad AFR exome AF: 0.00525

Gnomad AMR exome AF: 0.000955

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.0166

Gnomad SAS exome AF: 0.00577

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00140 AC: 2042 AN: 1460432 Hom.: 26 Cov.: 32 AF XY: 0.00155 AC XY: 1125 AN XY: 726560

Gnomad4 AFR exome AF: 0.00486

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00226

Gnomad4 EAS exome AF: 0.0168

Gnomad4 SAS exome AF: 0.00569

Gnomad4 FIN exome AF: 0.00116

Gnomad4 NFE exome AF: 0.000366

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00363 AC: 551 AN: 151880 Hom.: 4 Cov.: 31 AF XY: 0.00384 AC XY: 285 AN XY: 74226

Gnomad4 AFR AF: 0.00681

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0250

Gnomad4 SAS AF: 0.00750

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.000810

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00226 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Phe129Phe in exon 5 of SFTPA1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 4.0% (8/200) of Han Chinese chromosomes from a broad population by the 1000 Genomes Project (http:/ /www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs1059056). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1059056; hg19: chr10-81372994;