10-79611646-T-C

Variant names:

• chr10-79611646-T-C
• rs765560434
• NM_005411.5:c.-23-157T>C

Variant summary

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

The NM_005411.5(SFTPA1):​c.-23-157T>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFTPA1 NM_005411.5 intron
• Scores: Splicing: ADA: 0.0001130
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 0 publications found

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.-23-157T>C		intron_variant	Intron 2 of 5	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.-23-157T>C		intron_variant	Intron 2 of 5	1	NM_005411.5	ENSP00000381633.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000608 AC: 1 AN: 164554 AF XY: 0.0000114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.12e-7 AC: 1 AN: 1404018 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 693158

African (AFR) AF: 0.00 AC: 0 AN: 31860

American (AMR) AF: 0.00 AC: 0 AN: 35944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25214

East Asian (EAS) AF: 0.00 AC: 0 AN: 36072

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081802

Other (OTH) AF: 0.00 AC: 0 AN: 58140

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.62
PhyloP100		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.026
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: rs765560434; hg19: chr10-81371402;