rs2559729

chr10-79611973-C-Achr10-79611973-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005411.5(SFTPA1):c.148C>A(p.Leu50Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 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 NM_005411.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060816526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.148C>A	p.Leu50Ile	missense_variant	3/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.148C>A	p.Leu50Ile	missense_variant	3/6	1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.193C>A	p.Leu65Ile	missense_variant	3/6	1
SFTPA1	ENST00000428376.6	c.148C>A	p.Leu50Ile	missense_variant	2/5	1		P1
SFTPA1	ENST00000429958.5	c.148C>A	p.Leu50Ile	missense_variant	2/5	1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1436616 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 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.: 29

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	T
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	N
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.061	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.14	N;N;.;.;.
MutationTaster	Benign	0.81	D;N;N;N;N
PrimateAI	Uncertain	0.60	T
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	T
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

Other links and lift over

dbSNP: rs1136450; hg19: chr10-81371729;