chr1-110363793-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 12/15 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

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05328524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A4	NM_004696.3	c.1437C>T	p.Ala479Ala	synonymous_variant	Exon 9 of 9	ENST00000369779.9	NP_004687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A4	ENST00000369779.9	c.1437C>T	p.Ala479Ala	synonymous_variant	Exon 9 of 9	1	NM_004696.3	ENSP00000358794.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000162 AC: 4 AN: 246734 Hom.: 0 AF XY: 0.00000750 AC XY: 1 AN XY: 133328

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000991

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

EpiCase AF: 0.0000548

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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

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: rs777078429; hg19: chr1-110906415;