10-79613943-C-T

Variant names:

• chr10-79613943-C-T
• rs139806726
• NM_005411.5:c.577C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005411.5(SFTPA1):​c.577C>T​(p.Pro193Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.732
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• interstitial lung disease 1

  Inheritance: AD, SD Classification: STRONG, MODERATE Submitted by: ClinGen, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056151748).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005411.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA1	NM_005411.5	MANE Select	c.577C>T	p.Pro193Ser	missense	Exon 6 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.622C>T	p.Pro208Ser	missense	Exon 6 of 6	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.577C>T	p.Pro193Ser	missense	Exon 6 of 6	NP_001158116.1	Q8IWL2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA1	ENST00000398636.8	TSL:1 MANE Select	c.577C>T	p.Pro193Ser	missense	Exon 6 of 6	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.622C>T	p.Pro208Ser	missense	Exon 6 of 6	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.577C>T	p.Pro193Ser	missense	Exon 5 of 5	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000915 AC: 23 AN: 251422 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000237 AC: 346 AN: 1461770 Hom.: 0 Cov.: 33 AF XY: 0.000241 AC XY: 175 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000301 AC: 335 AN: 1111924

Other (OTH) AF: 0.000182 AC: 11 AN: 60382

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.3
DANN	Benign	0.29
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.30	N
PhyloP100		-0.73
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.0060
Sift	Benign	0.21	T
Sift4G	Benign	0.63	T
Polyphen		0.063	B
Vest4		0.11
MVP		0.14
MPC		0.96
ClinPred		0.049	T
GERP RS		-0.45
Varity_R		0.040
gMVP		0.39
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs139806726; hg19: chr10-81373699; COSMIC: COSV64867564; COSMIC: COSV64867564;