Variant 10-79611960-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_005411.5(SFTPA1):c.135C>T(p.Asp45Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,613,684 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 (no stars).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 4 hom. )

Consequence

SFTPA1
NM_005411.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0870

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-79611960-C-T is Benign according to our data. Variant chr10-79611960-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3055008.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-79611960-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.087 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5 link	c.135C>T	p.Asp45Asp	synonymous_variant	Exon 3 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.135C>T	p.Asp45Asp	synonymous_variant	Exon 3 of 6	1	NM_005411.5	ENSP00000381633.3	Q8IWL2-1
SFTPA1	ENST00000419470.6 link	c.180C>T	p.Asp60Asp	synonymous_variant	Exon 3 of 6	1		ENSP00000397082.2	Q8IWL2-2
SFTPA1	ENST00000428376.6 link	c.135C>T	p.Asp45Asp	synonymous_variant	Exon 2 of 5	1		ENSP00000411102.2	Q8IWL2-1
SFTPA1	ENST00000429958.5 link	c.135C>T	p.Asp45Asp	synonymous_variant	Exon 2 of 5	1		ENSP00000395527.1	A0A0C4DG36

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00519

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000964

GnomAD3 exomes

AF:

0.000734

AC:

184

AN:

250682

Hom.:

AF XY:

0.000760

AC XY:

103

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00504

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000320

AC:

467

AN:

1461582

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

234

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.00489

Gnomad4 NFE exome

AF:

0.0000836

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000454

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00519

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000954

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000567

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SFTPA1-related disorder

Benign:1

Feb 08, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.6

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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