rs16853149

Variant names:

• chr2-215019344-T-A
• rs16853149
• NM_173076.3:c.1649A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-215019344-T-A
• chr2-215019344-T-C
• chr2-215019344-T-G

Variant summary

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

The NM_173076.3(ABCA12):​c.1649A>T​(p.Glu550Val) variant causes a missense 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. 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. E550G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCA12 NM_173076.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 8 publications found

Genes affected

ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) 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, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ABCA12 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 4B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Orphanet, G2P
• autosomal recessive congenital ichthyosis 4A

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000227769 (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 (MetaRNN=0.050102055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.1649A>T	p.Glu550Val	missense_variant	Exon 13 of 53	ENST00000272895.12	NP_775099.2
ABCA12	NM_015657.4	c.695A>T	p.Glu232Val	missense_variant	Exon 5 of 45		NP_056472.2
ABCA12	XM_011510951.3	c.1649A>T	p.Glu550Val	missense_variant	Exon 13 of 53		XP_011509253.1
ABCA12	NR_103740.2	n.2091A>T		non_coding_transcript_exon_variant	Exon 14 of 55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.1649A>T	p.Glu550Val	missense_variant	Exon 13 of 53	1	NM_173076.3	ENSP00000272895.7
ABCA12	ENST00000389661.4	c.695A>T	p.Glu232Val	missense_variant	Exon 5 of 45	1		ENSP00000374312.4
ENSG00000227769	ENST00000617699.1	n.279-1380T>A		intron_variant	Intron 3 of 3	5
ENSG00000227769	ENST00000627811.1	n.74-3548T>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 95

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.73
DEOGEN2	Benign	0.089	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		-0.083
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.027
Sift	Benign	0.65	T;T
Sift4G	Uncertain	0.049	D;T
Polyphen		0.51	P;B
Vest4		0.30
MutPred		0.32		Gain of catalytic residue at E550 (P = 0.007);.;
MVP		0.30
MPC		0.22
ClinPred		0.099	T
GERP RS		0.17
Varity_R		0.065
gMVP		0.44
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs16853149; hg19: chr2-215884068;