Variant chr10-79559336-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001098668.4(SFTPA2):c.148G>A(p.Val50Ile) 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. 13/19 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. V50L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SFTPA2
NM_001098668.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

SFTPA2 (HGNC:10799): (surfactant protein A2) This gene is one of several genes encoding pulmonary-surfactant associated proteins (SFTPA) located on chromosome 10. Mutations in this gene and a highly similar gene located nearby, which affect the highly conserved carbohydrate recognition domain, are associated with idiopathic pulmonary fibrosis. The current version of the assembly displays only a single centromeric SFTPA gene pair rather than the two gene pairs shown in the previous assembly which were thought to have resulted from a duplication. [provided by RefSeq, Sep 2009]

SFTPA2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a chain Pulmonary surfactant-associated protein A2 (size 227) in uniprot entity SFPA2_HUMAN there are 11 pathogenic changes around while only 3 benign (79%) in NM_001098668.4

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.089821994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 linkuse as main transcript	c.148G>A	p.Val50Ile	missense_variant	3/6	ENST00000372325.7	NP_001092138.1	Q8IWL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SFTPA2	ENST00000372325.7 linkuse as main transcript	c.148G>A	p.Val50Ile	missense_variant	3/6	1	NM_001098668.4	ENSP00000361400.2	Q8IWL1
SFTPA2	ENST00000372327.9 linkuse as main transcript	c.148G>A	p.Val50Ile	missense_variant	2/5	1		ENSP00000361402.5	Q8IWL1
SFTPA2	ENST00000417041.1 linkuse as main transcript	c.148G>A	p.Val50Ile	missense_variant	3/6	5		ENSP00000397375.1	X6REF7
SFTPA2	ENST00000492049.1 linkuse as main transcript	c.148G>A	p.Val50Ile	missense_variant	1/2	5		ENSP00000473275.1	R4GMN3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.93e-7

AC:

AN:

1443698

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718688

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:

0.0000116

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

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.026

DANN

Benign

0.76

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.42

.;.;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.090

T;T;T;T

MetaSVM

Benign

-0.87

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.29

N;N;N;.

REVEL

Benign

0.022

Sift

Benign

0.50

T;T;T;.

Sift4G

Benign

0.49

T;T;T;.

Vest4

0.070

MutPred

0.37

Loss of methylation at R47 (P = 0.0849);Loss of methylation at R47 (P = 0.0849);Loss of methylation at R47 (P = 0.0849);Loss of methylation at R47 (P = 0.0849);

MVP

0.33

MPC

1.0

ClinPred

0.028

GERP RS

-4.2

gMVP

0.080

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