10-79612410-C-G

Position:

• chr10-79612410-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005411.5(SFTPA1):​c.271C>G​(p.Pro91Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 1,613,396 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (87 hom.)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.759

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01736933).
• BP6: Variant 10-79612410-C-G is Benign according to our data. Variant chr10-79612410-C-G is described in ClinVar as [Benign]. Clinvar id is 165198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-79612410-C-G is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.271C>G	p.Pro91Ala	missense_variant	4/6	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.271C>G	p.Pro91Ala	missense_variant	4/6	1	NM_005411.5	ENSP00000381633	P1
SFTPA1	ENST00000419470.6	c.316C>G	p.Pro106Ala	missense_variant	4/6	1		ENSP00000397082
SFTPA1	ENST00000428376.6	c.271C>G	p.Pro91Ala	missense_variant	3/5	1		ENSP00000411102	P1
SFTPA1	ENST00000429958.5	c.271C>G	p.Pro91Ala	missense_variant	3/5	1		ENSP00000395527

Frequencies

GnomAD3 genomes AF: 0.00867 AC: 1317 AN: 151876 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00459

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00995

Gnomad OTH AF: 0.00672

GnomAD3 exomes AF: 0.00704 AC: 1769 AN: 251330 Hom.: 9 AF XY: 0.00717 AC XY: 974 AN XY: 135838

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00860

Gnomad FIN exome AF: 0.00291

Gnomad NFE exome AF: 0.00913

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00924 AC: 13506 AN: 1461402 Hom.: 87 Cov.: 34 AF XY: 0.00924 AC XY: 6719 AN XY: 727030

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00436

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00855

Gnomad4 FIN exome AF: 0.00373

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00699

GnomAD4 genome AF: 0.00867 AC: 1318 AN: 151994 Hom.: 7 Cov.: 32 AF XY: 0.00797 AC XY: 592 AN XY: 74304

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00562

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00995

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.00678 Hom.: 2

Bravo AF: 0.00926

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.0138 AC: 61

ESP6500EA AF: 0.0109 AC: 94

ExAC AF: 0.00723 AC: 878

EpiCase AF: 0.0103

EpiControl AF: 0.00883

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	SFTPA1: BS1, BS2 -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Pro106Ala in exon 4 of SFTPA1: This variant is not expected to have clinical sig nificance because it has been identified in 1.4% (61/4406) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs1136452). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.15	T;T;.;.;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.48	.;T;T;.;T
MetaRNN	Benign	0.017	T;T;T;T;T
MetaSVM	Uncertain	0.040	D
MutationAssessor	Benign	1.6	L;L;.;.;.
MutationTaster	Benign	0.82	N;N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Uncertain	0.35
Sift	Benign	0.077	T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.016	B;B;.;.;.
Vest4		0.36
MVP		0.92
MPC		0.12
ClinPred		0.016	T
GERP RS		2.7
Varity_R		0.068
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1136452; hg19: chr10-81372166;