NM_003019.5:c.752-113C>A

Variant names:

• chr10-79938341-G-T
• rs2819098
• NM_003019.5:c.752-113C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003019.5(SFTPD):​c.752-113C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000136 in 732,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SFTPD NM_003019.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.752-113C>A		intron_variant	Intron 7 of 7	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.752-113C>A		intron_variant	Intron 7 of 7		XP_011538389.1
SFTPD	XM_011540088.3	c.635-113C>A		intron_variant	Intron 6 of 6		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.752-113C>A		intron_variant	Intron 7 of 7	1	NM_003019.5	ENSP00000361366.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000136 AC: 1 AN: 732642 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 375700

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17818

American (AMR) AF: 0.00 AC: 0 AN: 24962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15930

East Asian (EAS) AF: 0.00 AC: 0 AN: 34886

South Asian (SAS) AF: 0.00 AC: 0 AN: 55822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3194

European-Non Finnish (NFE) AF: 0.00000196 AC: 1 AN: 510214

Other (OTH) AF: 0.00 AC: 0 AN: 35626

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.063
DANN	Benign	0.55
PhyloP100		-1.9

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: rs2819098; hg19: chr10-81698097;