10-79612403-G-T

Position:

• chr10-79612403-G-T

Variant summary

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

The NM_005411.5(SFTPA1):​c.264G>T​(p.Lys88Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.264G>T	p.Lys88Asn	missense_variant	4/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.264G>T	p.Lys88Asn	missense_variant	4/6	1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.309G>T	p.Lys103Asn	missense_variant	4/6	1
SFTPA1	ENST00000428376.6	c.264G>T	p.Lys88Asn	missense_variant	3/5	1		P1
SFTPA1	ENST00000429958.5	c.264G>T	p.Lys88Asn	missense_variant	3/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251362 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135848

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461450 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727020

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000487 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;.;.;.
Eigen	Benign	0.14
Eigen_PC	Benign	-0.034
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.83	.;T;T;.;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Uncertain	2.1	M;M;.;.;.
MutationTaster	Benign	0.95	N;N;N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.5	D;D;N;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.048	D;D;D;D;D
Polyphen		1.0	D;D;.;.;.
Vest4		0.38
MutPred		0.56		Loss of ubiquitination at K88 (P = 0.002);Loss of ubiquitination at K88 (P = 0.002);.;Loss of ubiquitination at K88 (P = 0.002);Loss of ubiquitination at K88 (P = 0.002);
MVP		0.74
MPC		0.13
ClinPred		0.90	D
GERP RS		0.83
Varity_R		0.45
gMVP		0.34

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: rs1323157282; hg19: chr10-81372159;