Variant 10-79612403-G-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA1	NM_005411.5 linkuse as main transcript	c.264G>T	p.Lys88Asn	missense_variant	4/6	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8 linkuse as main transcript	c.264G>T	p.Lys88Asn	missense_variant	4/6	1	NM_005411.5	ENSP00000381633	P1	Q8IWL2-1
SFTPA1	ENST00000419470.6 linkuse as main transcript	c.309G>T	p.Lys103Asn	missense_variant	4/6	1		ENSP00000397082		Q8IWL2-2
SFTPA1	ENST00000428376.6 linkuse as main transcript	c.264G>T	p.Lys88Asn	missense_variant	3/5	1		ENSP00000411102	P1	Q8IWL2-1
SFTPA1	ENST00000429958.5 linkuse as main transcript	c.264G>T	p.Lys88Asn	missense_variant	3/5	1		ENSP00000395527

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251362

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135848

show subpopulations

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:

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727020

show subpopulations

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.:

Alfa

AF:

0.0000487

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

The c.264G>T (p.K88N) alteration is located in exon 4 (coding exon 2) of the SFTPA1 gene. This alteration results from a G to T substitution at nucleotide position 264, causing the lysine (K) at amino acid position 88 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;.;.;.

Eigen

Benign

0.14

Eigen_PC

Benign

-0.034

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.83

.;T;T;.;T

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.49

T;T;T;T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Uncertain

2.1

M;M;.;.;.

MutationTaster

Benign

0.95

N;N;N;N;N

PrimateAI

Uncertain

0.70

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over