rs17878336

Variant names:

• chr10-79942454-G-C
• rs17878336
• NM_003019.5:c.367C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-79942454-G-C
• chr10-79942454-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003019.5(SFTPD):​c.367C>G​(p.Leu123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,613,350 control chromosomes in the GnomAD database, including 1,112 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 0.026 (87 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1025 hom.)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.483
• Publications: 11 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=0.0068519413).
• BP6: Variant 10-79942454-G-C is Benign according to our data. Variant chr10-79942454-G-C is described in ClinVar as Benign. ClinVar VariationId is 165216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0265 (4026/152196) while in subpopulation AMR AF = 0.0451 (690/15288). AF 95% confidence interval is 0.0423. There are 87 homozygotes in GnomAd4. There are 1913 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 87 AR gene

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.367C>G	p.Leu123Val	missense	Exon 4 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.367C>G	p.Leu123Val	missense	Exon 4 of 8	ENSP00000361366.3
	SFTPD	ENST00000444384.3	TSL:3	c.406C>G	p.Leu136Val	missense	Exon 4 of 6	ENSP00000394325.1
	SFTPD	ENST00000678361.1		n.2255C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4029 AN: 152076 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0307

GnomAD2 exomes AF: 0.0257 AC: 6461 AN: 251036 AF XY: 0.0257

Gnomad AFR exome AF: 0.00770

Gnomad AMR exome AF: 0.0253

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0184

Gnomad NFE exome AF: 0.0373

Gnomad OTH exome AF: 0.0318

GnomAD4 exome AF: 0.0346 AC: 50500 AN: 1461154 Hom.: 1025 Cov.: 32 AF XY: 0.0339 AC XY: 24649 AN XY: 726780

African (AFR) AF: 0.00547 AC: 183 AN: 33474

American (AMR) AF: 0.0260 AC: 1161 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0376 AC: 983 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.00922 AC: 795 AN: 86256

European-Finnish (FIN) AF: 0.0194 AC: 1034 AN: 53352

Middle Eastern (MID) AF: 0.0140 AC: 81 AN: 5768

European-Non Finnish (NFE) AF: 0.0398 AC: 44278 AN: 1111412

Other (OTH) AF: 0.0329 AC: 1983 AN: 60362

GnomAD4 genome AF: 0.0265 AC: 4026 AN: 152196 Hom.: 87 Cov.: 32 AF XY: 0.0257 AC XY: 1913 AN XY: 74416

African (AFR) AF: 0.00734 AC: 305 AN: 41536

American (AMR) AF: 0.0451 AC: 690 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4826

European-Finnish (FIN) AF: 0.0168 AC: 178 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2567 AN: 68000

Other (OTH) AF: 0.0299 AC: 63 AN: 2110

Alfa AF: 0.0342 Hom.: 71

Bravo AF: 0.0271

TwinsUK AF: 0.0402 AC: 149

ALSPAC AF: 0.0444 AC: 171

ESP6500AA AF: 0.0109 AC: 48

ESP6500EA AF: 0.0409 AC: 352

ExAC AF: 0.0256 AC: 3105

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0372

EpiControl AF: 0.0381

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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.029
DANN	Benign	0.93
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.015	N
PhyloP100		-0.48
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.023
Sift	Benign	0.15	T
Sift4G	Benign	0.29	T
Polyphen		0.017	B
Vest4		0.086
MPC		0.17
ClinPred		0.0085	T
GERP RS		-6.7
Varity_R		0.043
gMVP		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: rs17878336; hg19: chr10-81702210;