1-110381127-G-C

Variant names:

• chr1-110381127-G-C
• rs377189979
• NM_004696.3:c.381C>G

Variant summary

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

The NM_004696.3(SLC16A4):​c.381C>G​(p.Phe127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000034 (0 hom.)
• Consequence: SLC16A4 NM_004696.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104326904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A4	NM_004696.3	c.381C>G	p.Phe127Leu	missense_variant	Exon 5 of 9	ENST00000369779.9	NP_004687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A4	ENST00000369779.9	c.381C>G	p.Phe127Leu	missense_variant	Exon 5 of 9	1	NM_004696.3	ENSP00000358794.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251306 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.381C>G (p.F127L) alteration is located in exon 5 (coding exon 4) of the SLC16A4 gene. This alteration results from a C to G substitution at nucleotide position 381, causing the phenylalanine (F) at amino acid position 127 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.035	T;.;.;.;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T;T;T;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.72	N;.;.;.;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	1.3	N;N;N;N;N
REVEL	Benign	0.033
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0010	B;.;.;.;.
Vest4		0.23
MutPred		0.67		Loss of catalytic residue at F127 (P = 0.1215);.;.;.;Loss of catalytic residue at F127 (P = 0.1215);
MVP		0.46
MPC		0.11
ClinPred		0.097	T
GERP RS		2.6
Varity_R		0.13
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs377189979; hg19: chr1-110923749;