NM_003019.5:c.538A>C

Variant names:

• chr10-79941966-T-G
• rs2243639
• NM_003019.5:c.538A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003019.5(SFTPD):​c.538A>C​(p.Thr180Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T180A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 87 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11652291).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPD	NM_003019.5	MANE Select	c.538A>C	p.Thr180Pro	missense	Exon 5 of 8	NP_003010.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPD	ENST00000372292.8	TSL:1 MANE Select	c.538A>C	p.Thr180Pro	missense	Exon 5 of 8	ENSP00000361366.3
	SFTPD	ENST00000444384.3	TSL:3	c.577A>C	p.Thr193Pro	missense	Exon 5 of 6	ENSP00000394325.1
	SFTPD	ENST00000678361.1		n.2743A>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	2.7
DANN	Benign	0.64
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-2.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.73	N
REVEL	Uncertain	0.36
Sift	Benign	0.43	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.057
MutPred		0.23		Loss of phosphorylation at T180 (P = 0.0176)
MVP		0.61
MPC		0.22
ClinPred		0.062	T
GERP RS		-3.8
Varity_R		0.10
gMVP		0.18
Mutation Taster		=99/1	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

dbSNP: rs2243639; hg19: chr10-81701722;