Menu
GeneBe

rs17885228

chr10-79942782-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_003019.5(SFTPD):c.297G>A(p.Lys99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,612,094 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.033 ( 136 hom., cov: 32)
Exomes 𝑓: 0.017 ( 318 hom. )

Consequence

SFTPD
NM_003019.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.138
Variant links:
Genes affected
SFTPD (HGNC:10803): (surfactant protein D) The protein encoded by this gene is part of the innate immune response, protecting the lungs against inhaled microorganisms and chemicals. The encoded protein may also be involved in surfactant metabolism. [provided by RefSeq, Jul 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-79942782-C-T is Benign according to our data. Variant chr10-79942782-C-T is described in ClinVar as [Benign]. Clinvar id is 165217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-79942782-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.138 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFTPDNM_003019.5 linkuse as main transcriptc.297G>A p.Lys99= synonymous_variant 3/8 ENST00000372292.8
SFTPDXM_011540087.2 linkuse as main transcriptc.297G>A p.Lys99= synonymous_variant 3/8
SFTPDXM_011540088.3 linkuse as main transcriptc.297G>A p.Lys99= synonymous_variant 3/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFTPDENST00000372292.8 linkuse as main transcriptc.297G>A p.Lys99= synonymous_variant 3/81 NM_003019.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0329
AC:
5006
AN:
152140
Hom.:
133
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0759
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.0289
Gnomad ASJ
AF:
0.0190
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.00600
Gnomad FIN
AF:
0.00226
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0175
Gnomad OTH
AF:
0.0421
GnomAD3 exomes
AF:
0.0176
AC:
4436
AN:
251436
Hom.:
64
AF XY:
0.0171
AC XY:
2326
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.0720
Gnomad AMR exome
AF:
0.0176
Gnomad ASJ exome
AF:
0.0195
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00728
Gnomad FIN exome
AF:
0.00245
Gnomad NFE exome
AF:
0.0180
Gnomad OTH exome
AF:
0.0217
GnomAD4 exome
AF:
0.0171
AC:
25025
AN:
1459836
Hom.:
318
Cov.:
31
AF XY:
0.0169
AC XY:
12264
AN XY:
726366
show subpopulations
Gnomad4 AFR exome
AF:
0.0767
Gnomad4 AMR exome
AF:
0.0179
Gnomad4 ASJ exome
AF:
0.0193
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00807
Gnomad4 FIN exome
AF:
0.00296
Gnomad4 NFE exome
AF:
0.0168
Gnomad4 OTH exome
AF:
0.0229
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0330
AC:
5024
AN:
152258
Hom.:
136
Cov.:
32
AF XY:
0.0322
AC XY:
2399
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0762
Gnomad4 AMR
AF:
0.0289
Gnomad4 ASJ
AF:
0.0190
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.00601
Gnomad4 FIN
AF:
0.00226
Gnomad4 NFE
AF:
0.0175
Gnomad4 OTH
AF:
0.0417
Alfa
AF:
0.0233
Hom.:
85
Bravo
AF:
0.0359
Asia WGS
AF:
0.0120
AC:
41
AN:
3478
EpiCase
AF:
0.0221
EpiControl
AF:
0.0251

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 21, 2013Lys99Lys in exon 3 of SFTPD: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 7.5% (331/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17885228). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
Cadd
Benign
6.5
Dann
Benign
0.67

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.

Other links and lift over

dbSNP: rs17885228; hg19: chr10-81702538; API