chr1-110379330-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004696.3(SLC16A4):​c.553G>A​(p.Ala185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,602,770 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.014 ( 50 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 39 hom. )

Consequence

SLC16A4
NM_004696.3 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.30
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0023040175).
BP6
Variant 1-110379330-C-T is Benign according to our data. Variant chr1-110379330-C-T is described in ClinVar as [Benign]. Clinvar id is 769522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2177/152236) while in subpopulation AFR AF= 0.0498 (2067/41522). AF 95% confidence interval is 0.048. There are 50 homozygotes in gnomad4. There are 1042 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC16A4NM_004696.3 linkc.553G>A p.Ala185Thr missense_variant Exon 6 of 9 ENST00000369779.9 NP_004687.1 O15374-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC16A4ENST00000369779.9 linkc.553G>A p.Ala185Thr missense_variant Exon 6 of 9 1 NM_004696.3 ENSP00000358794.4 O15374-1

Frequencies

GnomAD3 genomes
AF:
0.0143
AC:
2177
AN:
152118
Hom.:
50
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0499
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00439
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00716
GnomAD3 exomes
AF:
0.00372
AC:
927
AN:
249224
Hom.:
14
AF XY:
0.00282
AC XY:
380
AN XY:
134810
show subpopulations
Gnomad AFR exome
AF:
0.0488
Gnomad AMR exome
AF:
0.00255
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000165
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000284
Gnomad OTH exome
AF:
0.00181
GnomAD4 exome
AF:
0.00157
AC:
2279
AN:
1450534
Hom.:
39
Cov.:
32
AF XY:
0.00139
AC XY:
1003
AN XY:
719260
show subpopulations
Gnomad4 AFR exome
AF:
0.0505
Gnomad4 AMR exome
AF:
0.00252
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000247
Gnomad4 OTH exome
AF:
0.00318
GnomAD4 genome
AF:
0.0143
AC:
2177
AN:
152236
Hom.:
50
Cov.:
32
AF XY:
0.0140
AC XY:
1042
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0498
Gnomad4 AMR
AF:
0.00438
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00709
Alfa
AF:
0.00267
Hom.:
11
Bravo
AF:
0.0162
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0502
AC:
221
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.00462
AC:
561
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 05, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
13
DANN
Benign
0.71
DEOGEN2
Benign
0.045
T;.;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.74
T;T;T;T
MetaRNN
Benign
0.0023
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.14
N;.;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.010
N;N;N;N
REVEL
Benign
0.035
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.95
T;T;T;T
Polyphen
0.0010
B;.;.;.
Vest4
0.017
MVP
0.27
MPC
0.089
ClinPred
0.0028
T
GERP RS
-1.7
Varity_R
0.061
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35157487; hg19: chr1-110921952; API