rs756112668

Variant names:

• chr14-60982529-C-G
• rs756112668
• NM_153811.3:c.127C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-60982529-C-G
• chr14-60982529-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153811.3(SLC38A6):​c.127C>G​(p.Pro43Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P43S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC38A6 NM_153811.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 0 publications found

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]

ENSG00000258892 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048280567).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153811.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A6	NM_153811.3	MANE Select	c.127C>G	p.Pro43Ala	missense	Exon 2 of 16	NP_722518.2	Q8IZM9-1
	SLC38A6	NM_001172702.2		c.127C>G	p.Pro43Ala	missense	Exon 2 of 17	NP_001166173.1	Q8IZM9-2
	SLC38A6	NR_033344.2		n.469C>G		non_coding_transcript_exon	Exon 2 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A6	ENST00000267488.9	TSL:1 MANE Select	c.127C>G	p.Pro43Ala	missense	Exon 2 of 16	ENSP00000267488.4	Q8IZM9-1
	SLC38A6	ENST00000354886.6	TSL:1	c.127C>G	p.Pro43Ala	missense	Exon 2 of 17	ENSP00000346959.2	Q8IZM9-2
	SLC38A6	ENST00000451406.5	TSL:1	c.112C>G	p.Pro38Ala	missense	Exon 2 of 17	ENSP00000395851.1	A0A0C4DG39

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460276 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726242

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111630

Other (OTH) AF: 0.00 AC: 0 AN: 60328

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.4
DANN	Benign	0.72
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.21
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.015
Sift	Benign	0.15	T
Sift4G	Uncertain	0.058	T
Polyphen		0.14	B
Vest4		0.17
MVP		0.055
MPC		0.018
ClinPred		0.053	T
GERP RS		-0.71
PromoterAI		0.016	Neutral
Varity_R		0.043
gMVP		0.17
Mutation Taster		=95/5	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

dbSNP: rs756112668; hg19: chr14-61449247;