14-60981344-G-A

Position:

• chr14-60981344-G-A

Variant summary

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

The NM_153811.3(SLC38A6):​c.67G>A​(p.Glu23Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC38A6 NM_153811.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

Genes affected

SLC38A6 (HGNC:19863): (solute carrier family 38 member 6) Predicted to enable L-glutamine transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and glutamine transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRMT5 (HGNC:):

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=0.16409478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A6	NM_153811.3	c.67G>A	p.Glu23Lys	missense_variant	1/16	ENST00000267488.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A6	ENST00000267488.9	c.67G>A	p.Glu23Lys	missense_variant	1/16	1	NM_153811.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2023

The c.67G>A (p.E23K) alteration is located in exon 1 (coding exon 1) of the SLC38A6 gene. This alteration results from a G to A substitution at nucleotide position 67, causing the glutamic acid (E) at amino acid position 23 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;T
Eigen	Benign	0.088
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	M;M;.
MutationTaster	Benign	0.80	D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.55	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.93	P;B;.
Vest4		0.25
MutPred		0.44		Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);.;
MVP		0.10
MPC		0.038
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.33
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr14-61448062;