3-122806863-G-T

Variant names:

• chr3-122806863-G-T
• NM_032839.3:c.350G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032839.3(SLC49A4):​c.350G>T​(p.Arg117Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC49A4 NM_032839.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91

Genes affected

SLC49A4 (HGNC:16628): (solute carrier family 49 member 4) This gene encodes a membrane-bound protein from the major facilitator superfamily of transporters. Disruption of this gene by translocation has been associated with haplo-insufficiency and renal cell carcinomas. Alternatively spliced transcript variants have been described, but their biological validity has not yet been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC49A4	NM_032839.3	c.350G>T	p.Arg117Leu	missense_variant	Exon 2 of 9	ENST00000261038.6	NP_116228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC49A4	ENST00000261038.6	c.350G>T	p.Arg117Leu	missense_variant	Exon 2 of 9	1	NM_032839.3	ENSP00000261038.5
SLC49A4	ENST00000477647.1	n.343+11328G>T		intron_variant	Intron 1 of 7	1		ENSP00000418554.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.350G>T (p.R117L) alteration is located in exon 2 (coding exon 2) of the DIRC2 gene. This alteration results from a G to T substitution at nucleotide position 350, causing the arginine (R) at amino acid position 117 to be replaced by a leucine (L). 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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	30
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.030	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Vest4		0.94
MutPred		0.79		Loss of MoRF binding (P = 0.0371);
MVP		0.60
MPC		1.1
ClinPred		1.0	D
GERP RS		4.8
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-122525710;