chr1-110363793-G-A

Variant names:

• chr1-110363793-G-A
• rs777078429
• NM_004696.3:c.1437C>T

Variant summary

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

The NM_001201548.2(SLC16A4):​c.1127C>T​(p.Pro376Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,457,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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. P376R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SLC16A4 NM_001201548.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• 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: 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=0.05328524).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201548.2. 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.1437C>T	p.Ala479Ala	synonymous	Exon 9 of 9	NP_004687.1	O15374-1
	SLC16A4	NM_001201548.2		c.1127C>T	p.Pro376Leu	missense	Exon 7 of 7	NP_001188477.1	O15374-4
	SLC16A4	NM_001201546.2		c.1293C>T	p.Ala431Ala	synonymous	Exon 8 of 8	NP_001188475.1	O15374-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A4	ENST00000369779.9	TSL:1 MANE Select	c.1437C>T	p.Ala479Ala	synonymous	Exon 9 of 9	ENSP00000358794.4	O15374-1
	SLC16A4	ENST00000472422.6	TSL:1	c.1293C>T	p.Ala431Ala	synonymous	Exon 8 of 8	ENSP00000432495.1	O15374-5
	SLC16A4	ENST00000369781.8	TSL:1	c.933C>T	p.Ala311Ala	synonymous	Exon 8 of 8	ENSP00000358796.4	O15374-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 246734 AF XY: 0.00000750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1457114 Hom.: 0 Cov.: 31 AF XY: 0.00000690 AC XY: 5 AN XY: 724738

African (AFR) AF: 0.00 AC: 0 AN: 33094

American (AMR) AF: 0.0000227 AC: 1 AN: 43986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 85020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000991 AC: 11 AN: 1110288

Other (OTH) AF: 0.0000166 AC: 1 AN: 60148

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000548

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.5
DANN	Benign	0.31
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.92	T
PhyloP100		1.7
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.016
Sift	Benign	0.069	T
Sift4G	Benign	0.40	T
Vest4		0.061
MutPred		0.42		Loss of loop (P = 0.0235)
MVP		0.20
ClinPred		0.044	T
GERP RS		0.67
Mutation Taster		=92/8	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: rs777078429; hg19: chr1-110906415; COSMIC: COSV106528583;