Variant rs1136450 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000398636.8(SFTPA1):c.148C>A(p.Leu50Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. L50V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SFTPA1
ENST00000398636.8 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060816526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA1	NM_005411.5 linkuse as main transcript	c.148C>A	p.Leu50Ile	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>A	p.Leu50Ile	missense_variant	3/6	1	NM_005411.5	ENSP00000381633	P1	Q8IWL2-1
SFTPA1	ENST00000419470.6 linkuse as main transcript	c.193C>A	p.Leu65Ile	missense_variant	3/6	1		ENSP00000397082		Q8IWL2-2
SFTPA1	ENST00000428376.6 linkuse as main transcript	c.148C>A	p.Leu50Ile	missense_variant	2/5	1		ENSP00000411102	P1	Q8IWL2-1
SFTPA1	ENST00000429958.5 linkuse as main transcript	c.148C>A	p.Leu50Ile	missense_variant	2/5	1		ENSP00000395527

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1436616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715414

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.12

DANN

Benign

0.73

DEOGEN2

Benign

0.047

T;T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.47

.;T;T;.;T

M_CAP

Benign

0.00093

MetaRNN

Benign

0.061

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.14

N;N;.;.;.

MutationTaster

Benign

0.81

D;N;N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.34

N;N;N;N;N

REVEL

Benign

0.046

Sift

Benign

0.55

T;T;T;T;T

Sift4G

Benign

0.49

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.10

MutPred

0.20

Gain of methylation at K51 (P = 0.0592);Gain of methylation at K51 (P = 0.0592);.;Gain of methylation at K51 (P = 0.0592);Gain of methylation at K51 (P = 0.0592);

MVP

0.076

MPC

0.017

ClinPred

0.030

GERP RS

-3.0

Varity_R

0.043

gMVP

0.069

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over