10-79941974-G-C

Position:

• chr10-79941974-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 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

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 Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a modified_residue 4-hydroxyproline (size 0) in uniprot entity SFTPD_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.530C>G	p.Pro177Arg	missense_variant	5/8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.530C>G	p.Pro177Arg	missense_variant	5/8		XP_011538389.1
SFTPD	XM_011540088.3	c.413C>G	p.Pro138Arg	missense_variant	4/7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.530C>G	p.Pro177Arg	missense_variant	5/8	1	NM_003019.5	ENSP00000361366	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.530C>G (p.P177R) alteration is located in exon 5 (coding exon 4) of the SFTPD gene. This alteration results from a C to G substitution at nucleotide position 530, causing the proline (P) at amino acid position 177 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.94	D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D;N
REVEL	Uncertain	0.46
Sift	Benign	0.28	T;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-81701730;