rs1059058

Positions:

• chr10-79613972-C-T

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.606C>T​(p.Asp202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,610,506 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (44 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (45 hom.)
• Consequence: SFTPA1 NM_005411.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0960

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 10-79613972-C-T is Benign according to our data. Variant chr10-79613972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.096 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2180/151926) while in subpopulation AFR AF= 0.0494 (2045/41392). AF 95% confidence interval is 0.0476. There are 44 homozygotes in gnomad4. There are 1009 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 44 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.606C>T	p.Asp202=	synonymous_variant	6/6	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.606C>T	p.Asp202=	synonymous_variant	6/6	1	NM_005411.5	ENSP00000381633	P1
SFTPA1	ENST00000419470.6	c.651C>T	p.Asp217=	synonymous_variant	6/6	1		ENSP00000397082
SFTPA1	ENST00000428376.6	c.606C>T	p.Asp202=	synonymous_variant	5/5	1		ENSP00000411102	P1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2173 AN: 151810 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00137 AC: 343 AN: 250714 Hom.: 16 AF XY: 0.00116 AC XY: 157 AN XY: 135600

Gnomad AFR exome AF: 0.0186

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.000788 AC: 1149 AN: 1458580 Hom.: 45 Cov.: 33 AF XY: 0.000761 AC XY: 552 AN XY: 725832

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000454

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.0143 AC: 2180 AN: 151926 Hom.: 44 Cov.: 32 AF XY: 0.0136 AC XY: 1009 AN XY: 74244

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000776

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00728 Hom.: 4

Bravo AF: 0.0157

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

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Asp217Asp in exon 6 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 5.1% (9/176) of Yor uba (Nigerian) chromosomes from a broad population by the 1000 Genomes Project ( http://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs1059058). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.70

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: rs1059058; hg19: chr10-81373728;