Genetic Variant SLC36A4:c.56-1422G>A (chr11-93187236-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_152313.4(SLC36A4):c.56-1422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 152,160 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 32)

Consequence

SLC36A4
NM_152313.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.158

Publications

4 publications found

Variant links:

Genes affected

SLC36A4 (HGNC:19660): (solute carrier family 36 member 4) SLC36A4 belongs to the SLC36 family of amino acid transporters based on sequence similarity with other family members (e.g., SLC36A1; MIM 606561). SLC36 proteins contain about 500 amino acids and have 9 to 11 transmembrane domains. Unlike other SLC36 family members, which are proton-coupled amino acid transporters, SLC36A4 is a high-affinity/low-capacity non-proton-coupled amino acid transporter (Pillai and Meredith, 2011 [PubMed 21097500]).[supplied by OMIM, Feb 2011]

SLC36A4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1907/152160) while in subpopulation AFR AF = 0.0434 (1801/41514). AF 95% confidence interval is 0.0417. There are 38 homozygotes in GnomAd4. There are 908 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC36A4	NM_152313.4 link	c.56-1422G>A	intron_variant	Intron 1 of 10	ENST00000326402.9	NP_689526.2
SLC36A4	NM_001286139.2 link	c.-321-1422G>A	intron_variant	Intron 1 of 10		NP_001273068.1
SLC36A4	XM_047426350.1 link	c.-2-1422G>A	intron_variant	Intron 1 of 10		XP_047282306.1
SLC36A4	XM_047426352.1 link	c.56-1422G>A	intron_variant	Intron 1 of 9		XP_047282308.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC36A4	ENST00000326402.9 link	c.56-1422G>A	intron_variant	Intron 1 of 10	1	NM_152313.4	ENSP00000317382.4
SLC36A4	ENST00000529184.5 link	c.-321-1422G>A	intron_variant	Intron 1 of 10	2		ENSP00000436570.1
SLC36A4	ENST00000524875.1 link	n.56-1422G>A	intron_variant	Intron 1 of 6	3		ENSP00000434879.1
SLC36A4	ENST00000527743.1 link	n.153-1422G>A	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1876

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0428

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00466

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0125

AC:

1907

AN:

152160

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

908

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0434

AC:

1801

AN:

41514

American (AMR)

AF:

0.00465

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67994

Other (OTH)

AF:

0.0114

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

101

202

303

404

505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00899

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.3

(source)

DANN

Benign

0.28

PhyloP100

0.16

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over