10-79612324-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005411.5(SFTPA1):c.185C>T(p.Pro62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,613,882 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P62P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (13 hom.)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.96

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02057147).
• BP6: Variant 10-79612324-C-T is Benign according to our data. Variant chr10-79612324-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 786416.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-79612324-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.185C>T	p.Pro62Leu	missense_variant	4/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.185C>T	p.Pro62Leu	missense_variant	4/6	1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.230C>T	p.Pro77Leu	missense_variant	4/6	1
SFTPA1	ENST00000428376.6	c.185C>T	p.Pro62Leu	missense_variant	3/5	1		P1
SFTPA1	ENST00000429958.5	c.185C>T	p.Pro62Leu	missense_variant	3/5	1

Frequencies

GnomAD3 genomes AF: 0.00288 AC: 438 AN: 152110 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00469

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00265 AC: 666 AN: 251464 Hom.: 1 AF XY: 0.00266 AC XY: 361 AN XY: 135904

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00460

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00424 AC: 6201 AN: 1461656 Hom.: 13 Cov.: 34 AF XY: 0.00411 AC XY: 2989 AN XY: 727116

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.000421

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00141

Gnomad4 NFE exome AF: 0.00515

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.00288 AC: 438 AN: 152226 Hom.: 2 Cov.: 32 AF XY: 0.00297 AC XY: 221 AN XY: 74438

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00469

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00370 Hom.: 1

Bravo AF: 0.00271

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00477 AC: 41

ExAC AF: 0.00245 AC: 297

EpiCase AF: 0.00376

EpiControl AF: 0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.030
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;.;.;.
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.13	N
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.021	T;T;T;T;T
MetaSVM	Uncertain	0.43	D
MutationAssessor	Benign	1.8	L;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D
REVEL	Uncertain	0.57
Sift	Benign	0.56	T;T;T;D;D
Sift4G	Benign	0.070	T;T;T;D;D
Polyphen		1.0	D;D;.;.;.
Vest4		0.46
MVP		0.92
MPC		0.14
ClinPred		0.058	T
GERP RS		2.7
Varity_R		0.15
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs151242911; hg19: chr10-81372080;