chr1-110363861-C-A

Variant names:

• chr1-110363861-C-A
• rs1412190446
• NM_004696.3:c.1369G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004696.3(SLC16A4):​c.1369G>T​(p.Gly457Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000082 (0 hom.)
• Consequence: SLC16A4 NM_004696.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14910296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004696.3. 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
	SLC16A4	NM_004696.3	MANE Select	c.1369G>T	p.Gly457Cys	missense	Exon 9 of 9	NP_004687.1	O15374-1
	SLC16A4	NM_001201546.2		c.1225G>T	p.Gly409Cys	missense	Exon 8 of 8	NP_001188475.1	O15374-5
	SLC16A4	NM_001201547.2		c.1183G>T	p.Gly395Cys	missense	Exon 8 of 8	NP_001188476.1	O15374-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A4	ENST00000369779.9	TSL:1 MANE Select	c.1369G>T	p.Gly457Cys	missense	Exon 9 of 9	ENSP00000358794.4	O15374-1
	SLC16A4	ENST00000472422.6	TSL:1	c.1225G>T	p.Gly409Cys	missense	Exon 8 of 8	ENSP00000432495.1	O15374-5
	SLC16A4	ENST00000369781.8	TSL:1	c.865G>T	p.Gly289Cys	missense	Exon 8 of 8	ENSP00000358796.4	O15374-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460512 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726564

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 85976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111470

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.9
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.19
Sift	Benign	0.34	T
Sift4G	Benign	0.32	T
Polyphen		0.023	B
Vest4		0.24
MutPred		0.54		Gain of glycosylation at S462 (P = 0.136)
MVP		0.78
MPC		0.10
ClinPred		0.95	D
GERP RS		2.9
Varity_R		0.10
gMVP		0.58
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1412190446; hg19: chr1-110906483;