rs150214547

Variant names:

• chr10-79613996-C-G
• rs150214547
• NM_005411.5:c.630C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-79613996-C-G
• chr10-79613996-C-T
• chr10-79613996-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM1 BP4_Strong BP6_Very_Strong

The NM_005411.5(SFTPA1):​c.630C>G​(p.Asn210Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,614,242 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. N210N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.741
• Publications: 1 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 -10 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 8 uncertain in NM_005411.5
• BP4: Computational evidence support a benign effect (MetaRNN=0.02393189).
• BP6: Variant 10-79613996-C-G is Benign according to our data. Variant chr10-79613996-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 227943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.630C>G	p.Asn210Lys	missense	Exon 6 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.675C>G	p.Asn225Lys	missense	Exon 6 of 6	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.630C>G	p.Asn210Lys	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.630C>G	p.Asn210Lys	missense	Exon 6 of 6	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.675C>G	p.Asn225Lys	missense	Exon 6 of 6	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.630C>G	p.Asn210Lys	missense	Exon 5 of 5	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 258 AN: 152244 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00593

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000457 AC: 115 AN: 251462 AF XY: 0.000383

Gnomad AFR exome AF: 0.00597

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000185 AC: 270 AN: 1461880 Hom.: 1 Cov.: 33 AF XY: 0.000180 AC XY: 131 AN XY: 727244

African (AFR) AF: 0.00562 AC: 188 AN: 33476

American (AMR) AF: 0.000402 AC: 18 AN: 44722

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

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

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

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1112006

Other (OTH) AF: 0.000497 AC: 30 AN: 60396

GnomAD4 genome AF: 0.00169 AC: 258 AN: 152362 Hom.: 1 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74496

African (AFR) AF: 0.00591 AC: 246 AN: 41590

American (AMR) AF: 0.000522 AC: 8 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000313 Hom.: 0

Bravo AF: 0.00195

ESP6500AA AF: 0.00545 AC: 24

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000593 AC: 72

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		-0.74
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.80		Gain of methylation at N210 (P = 0.0017)
MVP		0.69
MPC		1.4
ClinPred		0.11	T
GERP RS		-0.23
Varity_R		0.77
gMVP		0.79
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs150214547; hg19: chr10-81373752;