10-79613943-C-A

Variant names:

• chr10-79613943-C-A
• NM_005411.5:c.577C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_005411.5(SFTPA1):​c.577C>A​(p.Pro193Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a disulfide_bond (size 91) in uniprot entity SFTA1_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_005411.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088970006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.577C>A	p.Pro193Thr	missense_variant	Exon 6 of 6	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.577C>A	p.Pro193Thr	missense_variant	Exon 6 of 6	1	NM_005411.5	ENSP00000381633.3
SFTPA1	ENST00000419470.6	c.622C>A	p.Pro208Thr	missense_variant	Exon 6 of 6	1		ENSP00000397082.2
SFTPA1	ENST00000428376.6	c.577C>A	p.Pro193Thr	missense_variant	Exon 5 of 5	1		ENSP00000411102.2
SFTPA1	ENST00000429958.5	c.*103C>A		downstream_gene_variant		1		ENSP00000395527.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461770 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727196

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.9
DANN	Benign	0.18
DEOGEN2	Benign	0.031	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.71	.;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.018
Sift	Benign	0.079	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.71	P;P;.
Vest4		0.17
MutPred		0.27		Loss of phosphorylation at T190 (P = 0.0808);Loss of phosphorylation at T190 (P = 0.0808);.;
MVP		0.19
MPC		1.1
ClinPred		0.13	T
GERP RS		-0.45
Varity_R		0.060
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-81373699;