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GeneBe

10-79946525-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003019.5(SFTPD):c.135T>C(p.Ser45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,613,760 control chromosomes in the GnomAD database, including 3,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.048 ( 239 hom., cov: 33)
Exomes 𝑓: 0.063 ( 3282 hom. )

Consequence

SFTPD
NM_003019.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42
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 -15 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=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-79946525-A-G is Benign according to our data. Variant chr10-79946525-A-G is described in ClinVar as [Benign]. Clinvar id is 165218.Status of the report is criteria_provided_single_submitter, 1 stars.
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=1.42 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFTPDNM_003019.5 linkuse as main transcriptc.135T>C p.Ser45= synonymous_variant 2/8 ENST00000372292.8
SFTPDXM_011540087.2 linkuse as main transcriptc.135T>C p.Ser45= synonymous_variant 2/8
SFTPDXM_011540088.3 linkuse as main transcriptc.135T>C p.Ser45= synonymous_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFTPDENST00000372292.8 linkuse as main transcriptc.135T>C p.Ser45= synonymous_variant 2/81 NM_003019.5 P1
SFTPDENST00000444384.3 linkuse as main transcriptc.174T>C p.Ser58= synonymous_variant 2/63
ENST00000421889.1 linkuse as main transcriptn.334-3503A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0479
AC:
7278
AN:
151892
Hom.:
239
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0135
Gnomad AMI
AF:
0.0998
Gnomad AMR
AF:
0.0480
Gnomad ASJ
AF:
0.0721
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00852
Gnomad FIN
AF:
0.0352
Gnomad MID
AF:
0.0759
Gnomad NFE
AF:
0.0750
Gnomad OTH
AF:
0.0541
GnomAD3 exomes
AF:
0.0462
AC:
11604
AN:
251372
Hom.:
381
AF XY:
0.0458
AC XY:
6222
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.0128
Gnomad AMR exome
AF:
0.0332
Gnomad ASJ exome
AF:
0.0623
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00852
Gnomad FIN exome
AF:
0.0401
Gnomad NFE exome
AF:
0.0717
Gnomad OTH exome
AF:
0.0543
GnomAD4 exome
AF:
0.0634
AC:
92658
AN:
1461750
Hom.:
3282
Cov.:
32
AF XY:
0.0622
AC XY:
45200
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.0107
Gnomad4 AMR exome
AF:
0.0348
Gnomad4 ASJ exome
AF:
0.0604
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00892
Gnomad4 FIN exome
AF:
0.0405
Gnomad4 NFE exome
AF:
0.0743
Gnomad4 OTH exome
AF:
0.0562
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0479
AC:
7274
AN:
152010
Hom.:
239
Cov.:
33
AF XY:
0.0445
AC XY:
3308
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0135
Gnomad4 AMR
AF:
0.0479
Gnomad4 ASJ
AF:
0.0721
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00852
Gnomad4 FIN
AF:
0.0352
Gnomad4 NFE
AF:
0.0750
Gnomad4 OTH
AF:
0.0540
Alfa
AF:
0.0677
Hom.:
478
Bravo
AF:
0.0475
Asia WGS
AF:
0.00924
AC:
32
AN:
3478
EpiCase
AF:
0.0752
EpiControl
AF:
0.0739

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, 2013Ser45Ser in exon 2 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 6.8% (589/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs6413520). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
7.6
Dann
Benign
0.69

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: rs6413520; hg19: chr10-81706281; COSMIC: COSV64852944; API