10-79612410-C-G

Variant names:

• chr10-79612410-C-G
• rs1136452
• NM_005411.5:c.271C>G

Variant summary

Our verdict is Benign. The variant received -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. 12/21 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:5
• Conservation: PhyloP100: 0.759
• Publications: 12 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: Benign. The variant received -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 VariationId is 165198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AD,AR gene

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.271C>G	p.Pro91Ala	missense	Exon 4 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.316C>G	p.Pro106Ala	missense	Exon 4 of 6	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.271C>G	p.Pro91Ala	missense	Exon 4 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.271C>G	p.Pro91Ala	missense	Exon 4 of 6	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.316C>G	p.Pro106Ala	missense	Exon 4 of 6	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.271C>G	p.Pro91Ala	missense	Exon 3 of 5	ENSP00000411102.2	Q8IWL2-1

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

GnomAD2 exomes AF: 0.00704 AC: 1769 AN: 251330 AF XY: 0.00717

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 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

African (AFR) AF: 0.0125 AC: 417 AN: 33478

American (AMR) AF: 0.00320 AC: 143 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00436 AC: 114 AN: 26118

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39684

South Asian (SAS) AF: 0.00855 AC: 737 AN: 86248

European-Finnish (FIN) AF: 0.00373 AC: 199 AN: 53326

Middle Eastern (MID) AF: 0.00573 AC: 33 AN: 5762

European-Non Finnish (NFE) AF: 0.0103 AC: 11438 AN: 1111706

Other (OTH) AF: 0.00699 AC: 422 AN: 60376

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

African (AFR) AF: 0.0119 AC: 492 AN: 41464

American (AMR) AF: 0.00458 AC: 70 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00562 AC: 27 AN: 4806

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00995 AC: 676 AN: 67936

Other (OTH) AF: 0.00665 AC: 14 AN: 2104

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Interstitial lung disease 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.017	T
MetaSVM	Uncertain	0.040	D
MutationAssessor	Benign	1.6	L
PhyloP100		0.76
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.35
Sift	Benign	0.077	T
Sift4G	Benign	0.13	T
Polyphen		0.016	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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1136452; hg19: chr10-81372166;