chr7-48227350-C-T

Variant names:

• chr7-48227350-C-T
• rs757024901
• NM_152701.5:c.557C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152701.5(ABCA13):​c.557C>T​(p.Pro186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,575,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000081 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ABCA13 NM_152701.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

Genes affected

ABCA13 (HGNC:14638): (ATP binding cassette subfamily A member 13) In human, the ATP-binding cassette (ABC) family of transmembrane transporters has at least 48 genes and 7 gene subfamilies. This gene is a member of ABC gene subfamily A (ABCA). Genes within the ABCA family typically encode several thousand amino acids. Like other ABC transmembrane transporter proteins, this protein has 12 or more transmembrane alpha-helix domains that likely arrange to form a single central chamber with multiple substrate binding sites. It is also predicted to have two large extracellular domains and two nucleotide binding domains as is typical for ABCA proteins. Alternative splice variants have been described but their biological validity has not been demonstrated.[provided by RefSeq, Mar 2009]

ABCA13 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36300135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA13	NM_152701.5	c.557C>T	p.Pro186Leu	missense_variant	Exon 6 of 62	ENST00000435803.6	NP_689914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA13	ENST00000435803.6	c.557C>T	p.Pro186Leu	missense_variant	Exon 6 of 62	1	NM_152701.5	ENSP00000411096.1
ABCA13	ENST00000417403.5	n.557C>T		non_coding_transcript_exon_variant	Exon 6 of 18	2		ENSP00000409268.1

Frequencies

GnomAD3 genomes AF: 0.00000810 AC: 1 AN: 123432 Hom.: 0 Cov.: 31

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: 0.0000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248988 AF XY: 0.0000222

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: 0.0000464

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1451764 Hom.: 0 Cov.: 32 AF XY: 0.00000831 AC XY: 6 AN XY: 722052

African (AFR) AF: 0.0000302 AC: 1 AN: 33118

American (AMR) AF: 0.00 AC: 0 AN: 44200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.0000513 AC: 2 AN: 38996

South Asian (SAS) AF: 0.0000353 AC: 3 AN: 84946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1106068

Other (OTH) AF: 0.00 AC: 0 AN: 59864

GnomAD4 genome AF: 0.00000810 AC: 1 AN: 123432 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 59820

African (AFR) AF: 0.00 AC: 0 AN: 32494

American (AMR) AF: 0.00 AC: 0 AN: 11840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2942

East Asian (EAS) AF: 0.00 AC: 0 AN: 4174

South Asian (SAS) AF: 0.00 AC: 0 AN: 3800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.0000176 AC: 1 AN: 56876

Other (OTH) AF: 0.00 AC: 0 AN: 1588

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 31, 2022

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.94	T
PhyloP100		2.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Vest4		0.44
MutPred		0.52		Gain of helix (P = 0.062);
MVP		0.46
MPC		0.035
ClinPred		0.26	T
GERP RS		5.3
gMVP		0.14
Mutation Taster		=88/12	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: rs757024901; hg19: chr7-48266947;