Genetic Variant SLC44A3:p.Gly14Ala (chr1-94820962-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001114106.3(SLC44A3):c.41G>C(p.Gly14Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,551,000 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00099 ( 1 hom. )

Consequence

SLC44A3
NM_001114106.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005376041).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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>C	p.Gly14Ala	missense	Exon 2 of 15	NP_001107578.1	Q8N4M1-1
SLC44A3	NM_001258340.2		c.41G>C	p.Gly14Ala	missense	Exon 2 of 15	NP_001245269.1
SLC44A3	NM_001258341.2		c.41G>C	p.Gly14Ala	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>C	p.Gly14Ala	missense	Exon 2 of 15	ENSP00000271227.6	Q8N4M1-1
SLC44A3	ENST00000467909.5	TSL:1	c.-10+239G>C		intron	N/A	ENSP00000432789.1	Q8N4M1-2
SLC44A3	ENST00000958852.1		c.41G>C	p.Gly14Ala	missense	Exon 2 of 16	ENSP00000628911.1

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000518

AC:

AN:

156468

AF XY:

0.000494

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000987

AC:

1381

AN:

1398752

Hom.:

Cov.:

AF XY:

0.000984

AC XY:

679

AN XY:

689914

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31580

American (AMR)

AF:

0.000168

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:

0.0000609

AC:

AN:

49256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00123

AC:

1323

AN:

1078508

Other (OTH)

AF:

0.000776

AC:

AN:

57954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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

AF:

0.000637

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41534

American (AMR)

AF:

0.00196

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000934

Hom.:

Bravo

AF:

0.000752

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.000406

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.3

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.017

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.62

M_CAP

Benign

0.012

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.91

PhyloP100

0.66

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.31

REVEL

Benign

0.18

Sift

Benign

0.65

Sift4G

Benign

0.75

Polyphen

0.0010

Vest4

0.11

MVP

0.40

MPC

0.17

ClinPred

0.0012

GERP RS

-4.3

PromoterAI

-0.00090

Neutral

(source)

Varity_R

0.035

gMVP

0.45

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over