Genetic Variant SLC44A3:p.Gly14Glu (chr1-94820962-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001114106.3(SLC44A3):c.41G>A(p.Gly14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. G14A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SLC44A3
NM_001114106.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.656

Publications

5 publications found

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:):

SLC44A3-AS1 links:

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ACMG classification

Classification was made for transcript

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=0.03152865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114106.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC44A3	NM_001114106.3	MANE Select	c.41G>A	p.Gly14Glu	missense	Exon 2 of 15	NP_001107578.1	Q8N4M1-1
SLC44A3	NM_001258340.2		c.41G>A	p.Gly14Glu	missense	Exon 2 of 15	NP_001245269.1
SLC44A3	NM_001258341.2		c.41G>A	p.Gly14Glu	missense	Exon 2 of 15	NP_001245270.1	Q8N4M1-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC44A3	ENST00000271227.11	TSL:1 MANE Select	c.41G>A	p.Gly14Glu	missense	Exon 2 of 15	ENSP00000271227.6	Q8N4M1-1
SLC44A3	ENST00000467909.5	TSL:1	c.-10+239G>A		intron	N/A	ENSP00000432789.1	Q8N4M1-2
SLC44A3	ENST00000958852.1		c.41G>A	p.Gly14Glu	missense	Exon 2 of 16	ENSP00000628911.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000192

AC:

AN:

156468

AF XY:

0.0000121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1398764

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31580

American (AMR)

AF:

0.0000841

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35720

South Asian (SAS)

AF:

0.00

AC:

AN:

79188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078520

Other (OTH)

AF:

0.00

AC:

AN:

57954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.5

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.40

M_CAP

Benign

0.0097

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.95

PhyloP100

0.66

PrimateAI

Benign

0.42

PROVEAN

Benign

0.53

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.065

MutPred

0.24

Loss of sheet (P = 0.0181)

MVP

0.43

MPC

0.20

ClinPred

0.0074

GERP RS

-4.3

PromoterAI

0.017

Neutral

(source)

Varity_R

0.033

gMVP

0.46

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over