3-184187919-T-A

Variant names:

• chr3-184187919-T-A
• NM_018358.3:c.505T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018358.3(ABCF3):​c.505T>A​(p.Ser169Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCF3 NM_018358.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

Genes affected

ABCF3 (HGNC:72): (ATP binding cassette subfamily F member 3) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ATP-binding cassette proteins transport various molecules across extra- and intracellular membranes. The protein encoded by this gene displays antiviral effect against flaviviruses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1420497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCF3	NM_018358.3	c.505T>A	p.Ser169Thr	missense_variant	Exon 6 of 21	ENST00000429586.7	NP_060828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCF3	ENST00000429586.7	c.505T>A	p.Ser169Thr	missense_variant	Exon 6 of 21	1	NM_018358.3	ENSP00000411471.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.505T>A (p.S169T) alteration is located in exon 6 (coding exon 6) of the ABCF3 gene. This alteration results from a T to A substitution at nucleotide position 505, causing the serine (S) at amino acid position 169 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.083	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Uncertain	0.0085	D
MutationAssessor	Benign	1.1	L;.
PhyloP100		2.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.14	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0090	B;B
Vest4		0.26
MutPred		0.30		Gain of glycosylation at S169 (P = 0.0012);.;
MVP		0.86
MPC		0.25
ClinPred		0.45	T
GERP RS		4.4
Varity_R		0.10
gMVP		0.26
Mutation Taster		=80/20	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

hg19: chr3-183905707;