10-79558907-C-T

Variant names:

• chr10-79558907-C-T
• NM_001098668.4:c.271G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001098668.4(SFTPA2):​c.271G>A​(p.Ala91Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A91P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SFTPA2 NM_001098668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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 2 ACMG points.

• PM1: In a chain Pulmonary surfactant-associated protein A2 (size 227) in uniprot entity SFPA2_HUMAN there are 11 pathogenic changes around while only 3 benign (79%) in NM_001098668.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2106387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4	c.271G>A	p.Ala91Thr	missense_variant	Exon 4 of 6	ENST00000372325.7	NP_001092138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7	c.271G>A	p.Ala91Thr	missense_variant	Exon 4 of 6	1	NM_001098668.4	ENSP00000361400.2
SFTPA2	ENST00000372327.9	c.271G>A	p.Ala91Thr	missense_variant	Exon 3 of 5	1		ENSP00000361402.5
SFTPA2	ENST00000417041.1	c.271G>A	p.Ala91Thr	missense_variant	Exon 4 of 6	5		ENSP00000397375.1
SFTPA2	ENST00000492049.1	c.271G>A	p.Ala91Thr	missense_variant	Exon 2 of 2	5		ENSP00000473275.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461850 Hom.: 0 Cov.: 70 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	12
DANN	Benign	0.95
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Uncertain	0.90	.;.;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.57	T
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.030	N;N;N;.
REVEL	Benign	0.25
Sift	Benign	0.032	D;D;D;.
Sift4G	Benign	0.083	T;T;T;.
Vest4		0.15
MutPred		0.30		Gain of phosphorylation at A91 (P = 0.0061);Gain of phosphorylation at A91 (P = 0.0061);Gain of phosphorylation at A91 (P = 0.0061);Gain of phosphorylation at A91 (P = 0.0061);
MVP		0.16
MPC		0.0040
ClinPred		0.14	T
GERP RS		1.6
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-81318663;