rs1136452

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_005411.5(SFTPA1):​c.271C>A​(p.Pro91Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P91A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SFTPA1
NM_005411.5 missense

Scores

11
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.759
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.39399636).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SFTPA1NM_005411.5 linkc.271C>A p.Pro91Thr missense_variant 4/6 ENST00000398636.8 NP_005402.3 Q8IWL2-1A0A024QZP2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SFTPA1ENST00000398636.8 linkc.271C>A p.Pro91Thr missense_variant 4/61 NM_005411.5 ENSP00000381633.3 Q8IWL2-1
SFTPA1ENST00000419470.6 linkc.316C>A p.Pro106Thr missense_variant 4/61 ENSP00000397082.2 Q8IWL2-2
SFTPA1ENST00000428376.6 linkc.271C>A p.Pro91Thr missense_variant 3/51 ENSP00000411102.2 Q8IWL2-1
SFTPA1ENST00000429958.5 linkc.271C>A p.Pro91Thr missense_variant 3/51 ENSP00000395527.1 A0A0C4DG36

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151880
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251330
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461418
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727038
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151880
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74178
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T;.;.;.
Eigen
Benign
-0.060
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.38
N
LIST_S2
Uncertain
0.86
.;D;D;.;D
M_CAP
Uncertain
0.086
D
MetaRNN
Benign
0.39
T;T;T;T;T
MetaSVM
Uncertain
0.28
D
MutationAssessor
Benign
1.7
L;L;.;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.0
D;D;D;D;D
REVEL
Uncertain
0.47
Sift
Uncertain
0.018
D;D;D;T;T
Sift4G
Uncertain
0.026
D;D;D;T;T
Polyphen
0.83
P;P;.;.;.
Vest4
0.34
MutPred
0.39
Gain of phosphorylation at P91 (P = 0.0247);Gain of phosphorylation at P91 (P = 0.0247);.;Gain of phosphorylation at P91 (P = 0.0247);Gain of phosphorylation at P91 (P = 0.0247);
MVP
0.93
MPC
0.13
ClinPred
0.91
D
GERP RS
2.7
Varity_R
0.13
gMVP
0.30

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.

Other links and lift over

dbSNP: rs1136452; hg19: chr10-81372166; API