10-79557426-A-C

Variant names:

• chr10-79557426-A-C
• rs762395469
• NM_001098668.4:c.530T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001098668.4(SFTPA2):​c.530T>G​(p.Phe177Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SFTPA2 NM_001098668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62

Genes affected

SFTPA2 (HGNC:10799): (surfactant protein A2) This gene is one of several genes encoding pulmonary-surfactant associated proteins (SFTPA) located on chromosome 10. Mutations in this gene and a highly similar gene located nearby, which affect the highly conserved carbohydrate recognition domain, are associated with idiopathic pulmonary fibrosis. The current version of the assembly displays only a single centromeric SFTPA gene pair rather than the two gene pairs shown in the previous assembly which were thought to have resulted from a duplication. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a domain C-type lectin (size 116) in uniprot entity SFPA2_HUMAN there are 11 pathogenic changes around while only 0 benign (100%) in NM_001098668.4
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4	c.530T>G	p.Phe177Cys	missense_variant	Exon 6 of 6	ENST00000372325.7	NP_001092138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7	c.530T>G	p.Phe177Cys	missense_variant	Exon 6 of 6	1	NM_001098668.4	ENSP00000361400.2
SFTPA2	ENST00000372327.9	c.530T>G	p.Phe177Cys	missense_variant	Exon 5 of 5	1		ENSP00000361402.5
SFTPA2	ENST00000417041.1	c.*56T>G		downstream_gene_variant		5		ENSP00000397375.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	0.16
Eigen_PC	Benign	-0.039
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.74	T
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Vest4		0.45
MutPred		0.75		Loss of stability (P = 0.0442);Loss of stability (P = 0.0442);
MVP		0.60
MPC		2.4
ClinPred		0.96	D
GERP RS		3.0
gMVP		0.59

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: rs762395469; hg19: chr10-81317182;