10-79611973-C-G

Position:

chr10-79611973-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005411.5(SFTPA1):c.148C>G(p.Leu50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,322,774 control chromosomes in the GnomAD database, including 258,923 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 Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.52 ( 20962 hom., cov: 29)

Exomes 𝑓: 0.57 ( 237961 hom. )

Consequence

SFTPA1
NM_005411.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.893

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2757053E-4).

BP6

Variant 10-79611973-C-G is Benign according to our data. Variant chr10-79611973-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 227062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-79611973-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA1	NM_005411.5 linkuse as main transcript	c.148C>G	p.Leu50Val	missense_variant	3/6	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8 linkuse as main transcript	c.148C>G	p.Leu50Val	missense_variant	3/6	1	NM_005411.5	ENSP00000381633	P1	Q8IWL2-1
SFTPA1	ENST00000419470.6 linkuse as main transcript	c.193C>G	p.Leu65Val	missense_variant	3/6	1		ENSP00000397082		Q8IWL2-2
SFTPA1	ENST00000428376.6 linkuse as main transcript	c.148C>G	p.Leu50Val	missense_variant	2/5	1		ENSP00000411102	P1	Q8IWL2-1
SFTPA1	ENST00000429958.5 linkuse as main transcript	c.148C>G	p.Leu50Val	missense_variant	2/5	1		ENSP00000395527

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

78464

AN:

150688

Hom.:

20968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.737

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.480

GnomAD3 exomes

AF:

0.494

AC:

117251

AN:

237278

Hom.:

31599

AF XY:

0.492

AC XY:

63271

AN XY:

128564

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.266

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.563

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.503

GnomAD4 exome

AF:

0.573

AC:

671034

AN:

1171968

Hom.:

237961

Cov.:

AF XY:

0.565

AC XY:

333686

AN XY:

591048

show subpopulations

Gnomad4 AFR exome

AF:

0.450

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.429

Gnomad4 EAS exome

AF:

0.304

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.562

Gnomad4 NFE exome

AF:

0.623

Gnomad4 OTH exome

AF:

0.530

GnomAD4 genome

AF:

0.520

AC:

78474

AN:

150806

Hom.:

20962

Cov.:

AF XY:

0.512

AC XY:

37708

AN XY:

73612

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.441

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.575

Gnomad4 NFE

AF:

0.587

Gnomad4 OTH

AF:

0.475

Alfa

AF:

0.518

Hom.:

3611

Bravo

AF:

0.515

ExAC

AF:

0.496

AC:

60242

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 13680361) -
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

Mar 12, 2015

p.Leu65Val in exon 3 of SFTPA1: This variant is not expected to have clinical si gnificance it has been identified in 57% (36928/65022) of European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1136450). -

SFTPA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 2024

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

0.064

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.040

DANN

Benign

0.18

DEOGEN2

Benign

0.047

T;T;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.17

.;T;T;.;T

MetaRNN

Benign

0.00023

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.60

N;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.58

N;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.73

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.069

MPC

0.017

ClinPred

0.0099

GERP RS

-3.0

Varity_R

0.036

gMVP

0.096

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