rs141621969

Variant names:

• chr16-2300114-G-A
• rs141621969
• NM_001089.3:c.1502C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2300114-G-A
• chr16-2300114-G-T

Variant summary

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

The NM_001089.3(ABCA3):​c.1502C>T​(p.Ala501Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. A501E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: ABCA3 NM_001089.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• Publications: 10 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060337126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.1502C>T	p.Ala501Val	missense_variant	Exon 13 of 33	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.1502C>T	p.Ala501Val	missense_variant	Exon 13 of 33	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.1328C>T	p.Ala443Val	missense_variant	Exon 12 of 32	1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.2065C>T		non_coding_transcript_exon_variant	Exon 13 of 20	1

Frequencies

GnomAD3 genomes AF: 0.0000726 AC: 11 AN: 151566 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251412 AF XY: 0.0000294

Gnomad AFR exome AF: 0.0000615

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: 0.0000791

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000718 AC: 105 AN: 1461794 Hom.: 0 Cov.: 32 AF XY: 0.0000756 AC XY: 55 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000809 AC: 90 AN: 1112008

Other (OTH) AF: 0.000232 AC: 14 AN: 60394

GnomAD4 genome AF: 0.0000726 AC: 11 AN: 151566 Hom.: 0 Cov.: 30 AF XY: 0.0000541 AC XY: 4 AN XY: 73986

African (AFR) AF: 0.00 AC: 0 AN: 41192

American (AMR) AF: 0.00 AC: 0 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67914

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00000220 Hom.: 16

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.2
DANN	Benign	0.25
DEOGEN2	Benign	0.062	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.35	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	-1.4	N;.
PhyloP100		2.9
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.51	N;N
REVEL	Benign	0.20
Sift	Benign	0.42	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0	B;.
Vest4		0.12
MutPred		0.35		Gain of methylation at K503 (P = 0.0635);.;
MVP		0.65
MPC		0.23
ClinPred		0.067	T
GERP RS		0.86
Varity_R		0.013
gMVP		0.64
Mutation Taster		=100/0	polymorphism

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: rs141621969; hg19: chr16-2350115;