Variant 1-94824511-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001114106.3(SLC44A3):c.154T>C(p.Ser52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,607,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC44A3
NM_001114106.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

SLC44A3 (HGNC:28689): (solute carrier family 44 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC44A3 links:

SLC44A3-AS1 (HGNC:49057): (SLC44A3 antisense RNA 1)

SLC44A3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42377582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A3	NM_001114106.3 linkuse as main transcript	c.154T>C	p.Ser52Pro	missense_variant	3/15	ENST00000271227.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A3	ENST00000271227.11 linkuse as main transcript	c.154T>C	p.Ser52Pro	missense_variant	3/15	1	NM_001114106.3	P1	Q8N4M1-1
SLC44A3-AS1	ENST00000634339.1 linkuse as main transcript	n.178+30733A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454888

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724026

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.154T>C (p.S52P) alteration is located in exon 3 (coding exon 3) of the SLC44A3 gene. This alteration results from a T to C substitution at nucleotide position 154, causing the serine (S) at amino acid position 52 to be replaced by a proline (P). 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

Benign

0.31

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.84

T;T;D;D;T;T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.42

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.17

MutationTaster

Benign

0.98

D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

N;N;D;N;N;D;D

REVEL

Benign

0.27

Sift

Benign

0.037

D;D;D;D;D;D;D

Sift4G

Benign

0.12

T;T;T;T;T;D;T

Polyphen

0.036

B;P;.;.;.;.;B

Vest4

0.62

MutPred

0.52

.;Gain of relative solvent accessibility (P = 0.1571);.;Gain of relative solvent accessibility (P = 0.1571);.;.;.;

MVP

0.89

MPC

0.58

ClinPred

0.69

GERP RS

4.4

Varity_R

0.67

gMVP

0.94

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over