chr7-48239270-G-T

Variant names:

• chr7-48239270-G-T
• rs144218923
• NM_152701.5:c.927G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152701.5(ABCA13):​c.927G>T​(p.Met309Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,613,930 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: ABCA13 NM_152701.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020962).
• BP6: Variant 7-48239270-G-T is Benign according to our data. Variant chr7-48239270-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA13	NM_152701.5	c.927G>T	p.Met309Ile	missense_variant	Exon 9 of 62	ENST00000435803.6	NP_689914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA13	ENST00000435803.6	c.927G>T	p.Met309Ile	missense_variant	Exon 9 of 62	1	NM_152701.5	ENSP00000411096.1
ABCA13	ENST00000417403.5	n.*49G>T		non_coding_transcript_exon_variant	Exon 9 of 18	2		ENSP00000409268.1
ABCA13	ENST00000417403.5	n.*49G>T		3_prime_UTR_variant	Exon 9 of 18	2		ENSP00000409268.1

Frequencies

GnomAD3 genomes AF: 0.000684 AC: 104 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000638 AC: 159 AN: 249196 AF XY: 0.000592

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.00119 AC: 1742 AN: 1461656 Hom.: 4 Cov.: 31 AF XY: 0.00112 AC XY: 811 AN XY: 727106

Gnomad4 AFR exome AF: 0.000418 AC: 14 AN: 33480

Gnomad4 AMR exome AF: 0.000335 AC: 15 AN: 44720

Gnomad4 ASJ exome AF: 0.000268 AC: 7 AN: 26134

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86250

Gnomad4 FIN exome AF: 0.000169 AC: 9 AN: 53400

Gnomad4 NFE exome AF: 0.00148 AC: 1644 AN: 1111830

Gnomad4 Remaining exome AF: 0.000878 AC: 53 AN: 60374

GnomAD4 genome AF: 0.000676 AC: 103 AN: 152274 Hom.: 0 Cov.: 33 AF XY: 0.000564 AC XY: 42 AN XY: 74456

Gnomad4 AFR AF: 0.000241 AC: 0.000240639 AN: 0.000240639

Gnomad4 AMR AF: 0.000262 AC: 0.000261609 AN: 0.000261609

Gnomad4 ASJ AF: 0.000865 AC: 0.000864553 AN: 0.000864553

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000188 AC: 0.00018843 AN: 0.00018843

Gnomad4 NFE AF: 0.00123 AC: 0.00123486 AN: 0.00123486

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.000608

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000964 AC: 8

ExAC AF: 0.000562 AC: 68

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ABCA13: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	12
DANN	Uncertain	0.98
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.40	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.26	T
Vest4		0.28
MutPred		0.30		Gain of methylation at K308 (P = 0.0202);
MVP		0.52
MPC		0.028
ClinPred		0.038	T
GERP RS		1.7
gMVP		0.092
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144218923; hg19: chr7-48278867;