10-79938055-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003019.5(SFTPD):c.925G>A(p.Glu309Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,614,052 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.036 (330 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (290 hom.)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016386211).
• BP6: Variant 10-79938055-C-T is Benign according to our data. Variant chr10-79938055-C-T is described in ClinVar as [Benign]. Clinvar id is 165213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPD	NM_003019.5	c.925G>A	p.Glu309Lys	missense_variant	8/8	ENST00000372292.8
SFTPD	XM_011540087.2	c.925G>A	p.Glu309Lys	missense_variant	8/8
SFTPD	XM_011540088.3	c.808G>A	p.Glu270Lys	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPD	ENST00000372292.8	c.925G>A	p.Glu309Lys	missense_variant	8/8	1	NM_003019.5	P1
SFTPD	ENST00000678361.1	n.3130G>A		non_coding_transcript_exon_variant	4/4
SFTPD	ENST00000679234.1	n.3051G>A		non_coding_transcript_exon_variant	5/5
	ENST00000421889.1	n.234+1399C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5509 AN: 152110 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0106 AC: 2655 AN: 251448 Hom.: 134 AF XY: 0.00801 AC XY: 1089 AN XY: 135888

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.00636

Gnomad ASJ exome AF: 0.0223

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000739

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00446 AC: 6517 AN: 1461824 Hom.: 290 Cov.: 31 AF XY: 0.00396 AC XY: 2879 AN XY: 727206

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.00689

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000466

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.0363 AC: 5524 AN: 152228 Hom.: 330 Cov.: 32 AF XY: 0.0355 AC XY: 2641 AN XY: 74438

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00864 Hom.: 163

Bravo AF: 0.0415

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.119 AC: 526

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.0123 AC: 1490

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Glu309Lys in exon 8 of SFTPD: This variant is not expected to have clinical sign ificance because it has been identified in 11.9% (526/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs4469829). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	8.5
Dann	Benign	0.82
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.75	N
MutationTaster	Benign	0.92	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.063
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.041
MPC		0.19
ClinPred		0.010	T
GERP RS		4.5
Varity_R		0.24
gMVP		0.43

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: rs4469829; hg19: chr10-81697811;