NM_003019.5:c.297G>A

Variant names:

• chr10-79942782-C-T
• rs17885228
• NM_003019.5:c.297G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003019.5(SFTPD):​c.297G>A​(p.Lys99Lys) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.138
• Publications: 5 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 10-79942782-C-T is Benign according to our data. Variant chr10-79942782-C-T is described in ClinVar as Benign. ClinVar VariationId is 165217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.138 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003019.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPD	NM_003019.5	MANE Select	c.297G>A	p.Lys99Lys	synonymous	Exon 3 of 8	NP_003010.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPD	ENST00000372292.8	TSL:1 MANE Select	c.297G>A	p.Lys99Lys	synonymous	Exon 3 of 8	ENSP00000361366.3	P35247
	SFTPD	ENST00000946714.1		c.465G>A	p.Lys155Lys	synonymous	Exon 4 of 9	ENSP00000616773.1
	SFTPD	ENST00000946710.1		c.438G>A	p.Lys146Lys	synonymous	Exon 4 of 9	ENSP00000616769.1

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5006 AN: 152140 Hom.: 133 Cov.: 32

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

GnomAD2 exomes AF: 0.0176 AC: 4436 AN: 251436 AF XY: 0.0171

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 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

African (AFR) AF: 0.0767 AC: 2562 AN: 33422

American (AMR) AF: 0.0179 AC: 801 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 503 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00807 AC: 696 AN: 86212

European-Finnish (FIN) AF: 0.00296 AC: 158 AN: 53420

Middle Eastern (MID) AF: 0.0500 AC: 288 AN: 5760

European-Non Finnish (NFE) AF: 0.0168 AC: 18636 AN: 1110148

Other (OTH) AF: 0.0229 AC: 1380 AN: 60336

GnomAD4 genome AF: 0.0330 AC: 5024 AN: 152258 Hom.: 136 Cov.: 32 AF XY: 0.0322 AC XY: 2399 AN XY: 74446

African (AFR) AF: 0.0762 AC: 3167 AN: 41556

American (AMR) AF: 0.0289 AC: 442 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5156

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4826

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0175 AC: 1192 AN: 68018

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0217 Hom.: 171

Bravo AF: 0.0359

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0221

EpiControl AF: 0.0251

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.5
DANN	Benign	0.67
PhyloP100		0.14
Mutation Taster		=100/0	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: rs17885228; hg19: chr10-81702538;