chr10-79938055-C-T

Variant names:

• chr10-79938055-C-T
• rs4469829
• NM_003019.5:c.925G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.43
• Publications: 10 publications found

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]

ENSG00000283913 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.925G>A	p.Glu309Lys	missense_variant	Exon 8 of 8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.925G>A	p.Glu309Lys	missense_variant	Exon 8 of 8		XP_011538389.1
SFTPD	XM_011540088.3	c.808G>A	p.Glu270Lys	missense_variant	Exon 7 of 7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.925G>A	p.Glu309Lys	missense_variant	Exon 8 of 8	1	NM_003019.5	ENSP00000361366.3

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

GnomAD2 exomes AF: 0.0106 AC: 2655 AN: 251448 AF XY: 0.00801

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 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

African (AFR) AF: 0.130 AC: 4359 AN: 33478

American (AMR) AF: 0.00689 AC: 308 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 583 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000394 AC: 34 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5768

European-Non Finnish (NFE) AF: 0.000466 AC: 518 AN: 1111956

Other (OTH) AF: 0.0111 AC: 668 AN: 60396

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

African (AFR) AF: 0.124 AC: 5134 AN: 41508

American (AMR) AF: 0.0137 AC: 209 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68022

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0141 Hom.: 379

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
PhyloP100		1.4
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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4469829; hg19: chr10-81697811;