rs754714105

Variant names:

• chr16-2326201-C-G
• rs754714105
• NM_001089.3:c.128G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-2326201-C-G
• chr16-2326201-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2 PM5 PP3_Strong

The NM_001089.3(ABCA3):​c.128G>C​(p.Arg43Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43C) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCA3 NM_001089.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.67
• Publications: 8 publications found

Genes affected

ABCA3 (HGNC:33): (ATP binding cassette subfamily A member 3) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The full transporter encoded by this gene may be involved in development of resistance to xenobiotics and engulfment during programmed cell death. [provided by RefSeq, Jul 2008]

ABCA3 Gene-Disease associations (from GenCC):

• interstitial lung disease due to ABCA3 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-2326202-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 1767530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.986

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.128G>C	p.Arg43Pro	missense_variant	Exon 5 of 33	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.128G>C	p.Arg43Pro	missense_variant	Exon 5 of 33	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.128G>C	p.Arg43Pro	missense_variant	Exon 5 of 32	1		ENSP00000371818.3
ABCA3	ENST00000567910.1	c.128G>C	p.Arg43Pro	missense_variant	Exon 4 of 6	1		ENSP00000454397.1
ABCA3	ENST00000563623.5	n.691G>C		non_coding_transcript_exon_variant	Exon 5 of 20	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000204 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.;.
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Pathogenic	0.86	D
MetaRNN	Pathogenic	0.99	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.4	M;.;M
PhyloP100		6.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Pathogenic	0.96
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.95
MutPred		0.83		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.99
MPC		1.0
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.94
gMVP		0.98

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: rs754714105; hg19: chr16-2376202;