Variant 10-79611942-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005411.5(SFTPA1):c.117C>T(p.His39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,662 control chromosomes in the GnomAD database, including 15,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1289 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13796 hom. )

Consequence

SFTPA1
NM_005411.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.95

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 10-79611942-C-T is Benign according to our data. Variant chr10-79611942-C-T is described in ClinVar as [Benign]. Clinvar id is 227061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.95 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5 linkuse as main transcript	c.117C>T	p.His39=	synonymous_variant	3/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8 linkuse as main transcript	c.117C>T	p.His39=	synonymous_variant	3/6	1	NM_005411.5	P1	Q8IWL2-1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19044

AN:

151980

Hom.:

1288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0993

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.0907

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.142

AC:

35584

AN:

250976

Hom.:

2906

AF XY:

0.149

AC XY:

20160

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.0958

Gnomad AMR exome

AF:

0.0817

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.131

AC:

191713

AN:

1461564

Hom.:

13796

Cov.:

108

AF XY:

0.135

AC XY:

98271

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0949

Gnomad4 AMR exome

AF:

0.0836

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.125

AC:

19050

AN:

152098

Hom.:

1289

Cov.:

AF XY:

0.128

AC XY:

9532

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0992

Gnomad4 AMR

AF:

0.0907

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.139

Hom.:

518

Bravo

AF:

0.114

Asia WGS

AF:

0.196

AC:

681

AN:

3478

EpiCase

AF:

0.138

EpiControl

AF:

0.133

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 12, 2015

p.His54His in exon 3 of SFTPA1: This variant is not expected to have clinical si gnificance it has been identified in 12.8% (8563/66692) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs72659390). -

SFTPA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.1

DANN

Benign

0.61

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