rs1662395011

Variant names:

• chr1-110381654-G-A
• rs1662395011
• NM_004696.3:c.362C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004696.3(SLC16A4):​c.362C>T​(p.Pro121Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A4 NM_004696.3 missense, splice_region
• Scores: Splicing: ADA: 0.03415
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

Genes affected

SLC16A4 (HGNC:10925): (solute carrier family 16 member 4) Predicted to enable monocarboxylic acid transmembrane transporter activity. Predicted to be involved in monocarboxylic acid transport. Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LAMTOR5-AS1 (HGNC:40823): (LAMTOR5 and SLC16A4 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32697347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A4	NM_004696.3	c.362C>T	p.Pro121Leu	missense_variant, splice_region_variant	Exon 4 of 9	ENST00000369779.9	NP_004687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A4	ENST00000369779.9	c.362C>T	p.Pro121Leu	missense_variant, splice_region_variant	Exon 4 of 9	1	NM_004696.3	ENSP00000358794.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362C>T (p.P121L) alteration is located in exon 4 (coding exon 3) of the SLC16A4 gene. This alteration results from a C to T substitution at nucleotide position 362, causing the proline (P) at amino acid position 121 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	Benign	0.30
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.046	T;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.085
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.47	T;T;T
Polyphen		0.50	P;.;.
Vest4		0.20
MutPred		0.52		Gain of catalytic residue at P121 (P = 0.1547);.;Gain of catalytic residue at P121 (P = 0.1547);
MVP		0.77
MPC		0.12
ClinPred		0.36	T
GERP RS		4.0
Varity_R		0.18
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.034
dbscSNV1_RF	Benign	0.20
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

LitVar

Other links and lift over

dbSNP: rs1662395011; hg19: chr1-110924276;