chr10-79611798-T-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_005411.5(SFTPA1):​c.-23-5T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.21 ( 5 hom. )
Failed GnomAD Quality Control

Consequence

SFTPA1
NM_005411.5 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.9993
2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.30
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP6
Variant 10-79611798-T-A is Benign according to our data. Variant chr10-79611798-T-A is described in ClinVar as [Benign]. Clinvar id is 3355976.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SFTPA1NM_005411.5 linkuse as main transcriptc.-23-5T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000398636.8 NP_005402.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SFTPA1ENST00000398636.8 linkuse as main transcriptc.-23-5T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_005411.5 ENSP00000381633 P1Q8IWL2-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1596
AN:
107188
Hom.:
0
Cov.:
33
FAILED QC
Gnomad AFR
AF:
0.0126
Gnomad AMI
AF:
0.00899
Gnomad AMR
AF:
0.0125
Gnomad ASJ
AF:
0.00418
Gnomad EAS
AF:
0.0257
Gnomad SAS
AF:
0.00981
Gnomad FIN
AF:
0.0412
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0135
Gnomad OTH
AF:
0.0176
GnomAD4 exome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.206
AC:
181168
AN:
877824
Hom.:
5
Cov.:
105
AF XY:
0.197
AC XY:
86314
AN XY:
439148
show subpopulations
Gnomad4 AFR exome
AF:
0.0691
Gnomad4 AMR exome
AF:
0.0670
Gnomad4 ASJ exome
AF:
0.0569
Gnomad4 EAS exome
AF:
0.0690
Gnomad4 SAS exome
AF:
0.0582
Gnomad4 FIN exome
AF:
0.0396
Gnomad4 NFE exome
AF:
0.253
Gnomad4 OTH exome
AF:
0.150
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0149
AC:
1594
AN:
107304
Hom.:
0
Cov.:
33
AF XY:
0.0160
AC XY:
838
AN XY:
52510
show subpopulations
Gnomad4 AFR
AF:
0.0125
Gnomad4 AMR
AF:
0.0124
Gnomad4 ASJ
AF:
0.00418
Gnomad4 EAS
AF:
0.0257
Gnomad4 SAS
AF:
0.00981
Gnomad4 FIN
AF:
0.0412
Gnomad4 NFE
AF:
0.0135
Gnomad4 OTH
AF:
0.0173
Alfa
AF:
0.0874
Hom.:
0

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SFTPA1-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesSep 25, 2024This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
16
DANN
Benign
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.91
SpliceAI score (max)
0.65
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.65
Position offset: 2
DS_AL_spliceai
0.31
Position offset: 5

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.

Other links and lift over

dbSNP: rs3997775; hg19: chr10-81371554; COSMIC: COSV64866565; API