NM_003019.5:c.538A>G

Variant names:

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

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.538A>G​(p.Thr180Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,605,800 control chromosomes in the GnomAD database, including 325,312 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39961 hom., cov: 32)
  • Exomes 𝑓: 0.62 (285351 hom.)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.466303E-6).
• BP6: Variant 10-79941966-T-C is Benign according to our data. Variant chr10-79941966-T-C is described in ClinVar as Benign. ClinVar VariationId is 165215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 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.538A>G	p.Thr180Ala	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.538A>G	p.Thr180Ala	missense	Exon 5 of 8	ENSP00000361366.3	P35247
	SFTPD	ENST00000946714.1		c.706A>G	p.Thr236Ala	missense	Exon 6 of 9	ENSP00000616773.1
	SFTPD	ENST00000946710.1		c.679A>G	p.Thr227Ala	missense	Exon 6 of 9	ENSP00000616769.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107888 AN: 151984 Hom.: 39889 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.693

GnomAD2 exomes AF: 0.657 AC: 164431 AN: 250320 AF XY: 0.655

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.633

Gnomad EAS exome AF: 0.809

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.601

Gnomad OTH exome AF: 0.641

GnomAD4 exome AF: 0.623 AC: 905035 AN: 1453698 Hom.: 285351 Cov.: 33 AF XY: 0.625 AC XY: 452022 AN XY: 723626

African (AFR) AF: 0.942 AC: 31354 AN: 33294

American (AMR) AF: 0.616 AC: 27513 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 16634 AN: 26074

East Asian (EAS) AF: 0.758 AC: 30075 AN: 39652

South Asian (SAS) AF: 0.726 AC: 62479 AN: 86062

European-Finnish (FIN) AF: 0.608 AC: 32436 AN: 53310

Middle Eastern (MID) AF: 0.668 AC: 3765 AN: 5636

European-Non Finnish (NFE) AF: 0.599 AC: 661506 AN: 1104936

Other (OTH) AF: 0.654 AC: 39273 AN: 60050

GnomAD4 genome AF: 0.710 AC: 108028 AN: 152102 Hom.: 39961 Cov.: 32 AF XY: 0.711 AC XY: 52826 AN XY: 74350

African (AFR) AF: 0.928 AC: 38542 AN: 41534

American (AMR) AF: 0.662 AC: 10116 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3466

East Asian (EAS) AF: 0.790 AC: 4063 AN: 5140

South Asian (SAS) AF: 0.740 AC: 3558 AN: 4810

European-Finnish (FIN) AF: 0.596 AC: 6306 AN: 10578

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40921 AN: 67974

Other (OTH) AF: 0.697 AC: 1466 AN: 2102

Alfa AF: 0.633 Hom.: 135401

Bravo AF: 0.723

TwinsUK AF: 0.590 AC: 2188

ALSPAC AF: 0.612 AC: 2358

ESP6500AA AF: 0.924 AC: 4070

ESP6500EA AF: 0.610 AC: 5243

ExAC AF: 0.663 AC: 80494

Asia WGS AF: 0.790 AC: 2748 AN: 3478

EpiCase AF: 0.605

EpiControl AF: 0.598

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.19
DANN	Benign	0.52
DEOGEN2	Benign	0.25	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0000025	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.40	N
PhyloP100		-2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.28
Sift	Benign	1.0	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.010
MPC		0.17
ClinPred		0.0079	T
GERP RS		-3.8
Varity_R		0.046
gMVP		0.098
Mutation Taster		=99/1	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: rs2243639; hg19: chr10-81701722; COSMIC: COSV64853510;