chr16-2317335-G-A

Variant names:

• chr16-2317335-G-A
• rs13332514
• NM_001089.3:c.1059C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001089.3(ABCA3):​c.1059C>T​(p.Phe353Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,880 control chromosomes in the GnomAD database, including 16,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1626 hom., cov: 31)
  • Exomes 𝑓: 0.12 (14864 hom.)
• Consequence: ABCA3 NM_001089.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.597
• Publications: 23 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 16-2317335-G-A is Benign according to our data. Variant chr16-2317335-G-A is described in ClinVar as Benign. ClinVar VariationId is 178698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.597 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001089.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	NM_001089.3	MANE Select	c.1059C>T	p.Phe353Phe	synonymous	Exon 10 of 33	NP_001080.2	Q99758-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	ENST00000301732.10	TSL:1 MANE Select	c.1059C>T	p.Phe353Phe	synonymous	Exon 10 of 33	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.1059C>T	p.Phe353Phe	synonymous	Exon 10 of 32	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000563623.5	TSL:1	n.1622C>T		non_coding_transcript_exon	Exon 10 of 20

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18599 AN: 152024 Hom.: 1614 Cov.: 31

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.134

GnomAD2 exomes AF: 0.170 AC: 42768 AN: 251266 AF XY: 0.161

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.378

Gnomad FIN exome AF: 0.0941

Gnomad NFE exome AF: 0.0957

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.121 AC: 176631 AN: 1461740 Hom.: 14864 Cov.: 33 AF XY: 0.121 AC XY: 87800 AN XY: 727176

African (AFR) AF: 0.0835 AC: 2794 AN: 33478

American (AMR) AF: 0.393 AC: 17578 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2917 AN: 26136

East Asian (EAS) AF: 0.392 AC: 15558 AN: 39696

South Asian (SAS) AF: 0.174 AC: 15042 AN: 86248

European-Finnish (FIN) AF: 0.0914 AC: 4874 AN: 53304

Middle Eastern (MID) AF: 0.118 AC: 682 AN: 5768

European-Non Finnish (NFE) AF: 0.0987 AC: 109714 AN: 1111990

Other (OTH) AF: 0.124 AC: 7472 AN: 60396

GnomAD4 genome AF: 0.123 AC: 18646 AN: 152140 Hom.: 1626 Cov.: 31 AF XY: 0.129 AC XY: 9618 AN XY: 74374

African (AFR) AF: 0.0864 AC: 3587 AN: 41528

American (AMR) AF: 0.272 AC: 4159 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3462

East Asian (EAS) AF: 0.372 AC: 1914 AN: 5144

South Asian (SAS) AF: 0.174 AC: 840 AN: 4816

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10596

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6306 AN: 68008

Other (OTH) AF: 0.133 AC: 282 AN: 2114

Alfa AF: 0.0982 Hom.: 461

Bravo AF: 0.136

Asia WGS AF: 0.233 AC: 811 AN: 3478

EpiCase AF: 0.0985

EpiControl AF: 0.0951

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hereditary pulmonary alveolar proteinosis (1)
-	-	1	Interstitial lung disease due to ABCA3 deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		0.60
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: rs13332514; hg19: chr16-2367336; COSMIC: COSV57053979;