3-122795268-T-A

Variant names:

• chr3-122795268-T-A
• NM_032839.3:c.76T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032839.3(SLC49A4):​c.76T>A​(p.Ser26Thr) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC49A4 NM_032839.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.455

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0822711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC49A4	NM_032839.3	c.76T>A	p.Ser26Thr	missense_variant	Exon 1 of 9	ENST00000261038.6	NP_116228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC49A4	ENST00000261038.6	c.76T>A	p.Ser26Thr	missense_variant	Exon 1 of 9	1	NM_032839.3	ENSP00000261038.5
SLC49A4	ENST00000477647.1	n.76T>A		non_coding_transcript_exon_variant	Exon 1 of 8	1		ENSP00000418554.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76T>A (p.S26T) alteration is located in exon 1 (coding exon 1) of the DIRC2 gene. This alteration results from a T to A substitution at nucleotide position 76, causing the serine (S) at amino acid position 26 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	0.095
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.79
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.26	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.63	T
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.38	N
REVEL	Benign	0.16
Sift	Benign	0.18	T
Sift4G	Benign	0.41	T
Vest4		0.045
MutPred		0.22		Gain of glycosylation at S26 (P = 0.0072);
MVP		0.11
MPC		1.4
ClinPred		0.082	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
gMVP		0.33

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: chr3-122514115;