10-79614021-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_005411.5(SFTPA1):c.655C>T(p.Arg219Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 1,614,084 control chromosomes in the GnomAD database, including 7,308 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 750 hom., cov: 32)

Exomes 𝑓: 0.089 ( 6558 hom. )

Consequence

SFTPA1
NM_005411.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: -0.198

Variant links:

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]

SFTPA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a disulfide_bond (size 91) in uniprot entity SFTA1_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_005411.5

BP4

Computational evidence support a benign effect (MetaRNN=0.00728637).

BP6

Variant 10-79614021-C-T is Benign according to our data. Variant chr10-79614021-C-T is described in ClinVar as [Benign]. Clinvar id is 13206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5 link	c.655C>T	p.Arg219Trp	missense_variant	Exon 6 of 6	ENST00000398636.8	NP_005402.3	Q8IWL2-1A0A024QZP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFTPA1	ENST00000398636.8 link	c.655C>T	p.Arg219Trp	missense_variant	Exon 6 of 6	1	NM_005411.5	ENSP00000381633.3	Q8IWL2-1
SFTPA1	ENST00000419470.6 link	c.700C>T	p.Arg234Trp	missense_variant	Exon 6 of 6	1		ENSP00000397082.2	Q8IWL2-2
SFTPA1	ENST00000428376.6 link	c.655C>T	p.Arg219Trp	missense_variant	Exon 5 of 5	1		ENSP00000411102.2	Q8IWL2-1
SFTPA1	ENST00000429958.5 link	c.*181C>T		downstream_gene_variant		1		ENSP00000395527.1	A0A0C4DG36

Frequencies

GnomAD3 genomes

AF:

0.0921

AC:

14015

AN:

152094

Hom.:

749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0700

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0986

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0874

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.102

AC:

25641

AN:

251448

Hom.:

1639

AF XY:

0.0999

AC XY:

13578

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.0916

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.256

Gnomad SAS exome

AF:

0.0643

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0899

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0887

AC:

129695

AN:

1461870

Hom.:

6558

Cov.:

AF XY:

0.0882

AC XY:

64130

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0720

Gnomad4 AMR exome

AF:

0.0908

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.0644

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.0831

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.0921

AC:

14026

AN:

152214

Hom.:

750

Cov.:

AF XY:

0.0941

AC XY:

7003

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0700

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.0742

Gnomad4 FIN

AF:

0.0986

Gnomad4 NFE

AF:

0.0874

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.0793

Hom.:

258

Bravo

AF:

0.0930

TwinsUK

AF:

0.0828

AC:

307

ALSPAC

AF:

0.0823

AC:

317

ESP6500AA

AF:

0.0801

AC:

353

ESP6500EA

AF:

0.0868

AC:

746

ExAC

AF:

0.100

AC:

12177

Asia WGS

AF:

0.156

AC:

541

AN:

3478

EpiCase

AF:

0.0909

EpiControl

AF:

0.0984

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26792177, 13680361, 23926107, 16292672) -

Pulmonary fibrosis, idiopathic, susceptibility to

Uncertain:1

Nov 01, 2003

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified

Benign:1

Oct 11, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is frequent in the general population (MAF around 8%) -

SFTPA1-related disorder

Benign:1

Sep 10, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.1

DANN

Benign

0.75

DEOGEN2

Benign

0.16

T;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.75

.;T;T

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.82

L;L;.

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.061

Sift

Benign

0.060

T;T;T

Sift4G

Uncertain

0.048

D;D;D

Polyphen

0.026

B;B;.

Vest4

0.10

MPC

0.97

ClinPred

0.010

GERP RS

1.9

Varity_R

0.13

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over