NM_003019.5:c.530C>G

Variant names:

• chr10-79941974-G-C
• NM_003019.5:c.530C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003019.5(SFTPD):​c.530C>G​(p.Pro177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,470 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.530C>G	p.Pro177Arg	missense	Exon 5 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.530C>G	p.Pro177Arg	missense	Exon 5 of 8	ENSP00000361366.3	P35247
	SFTPD	ENST00000946714.1		c.698C>G	p.Pro233Arg	missense	Exon 6 of 9	ENSP00000616773.1
	SFTPD	ENST00000946710.1		c.671C>G	p.Pro224Arg	missense	Exon 6 of 9	ENSP00000616769.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460470 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726612

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110860

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	1.6	L
PhyloP100		3.0
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.46
Sift	Benign	0.28	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.31
MutPred		0.47		Gain of MoRF binding (P = 3e-04)
MVP		0.96
MPC		0.33
ClinPred		0.85	D
GERP RS		5.2
Varity_R		0.23
gMVP		0.23
Mutation Taster		=81/19	polymorphism

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

hg19: chr10-81701730;