11-93187236-C-T

Position:

• chr11-93187236-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC36A4	NM_152313.4	c.56-1422G>A		intron_variant		ENST00000326402.9
SLC36A4	NM_001286139.2	c.-321-1422G>A		intron_variant
SLC36A4	XM_047426350.1	c.-2-1422G>A		intron_variant
SLC36A4	XM_047426352.1	c.56-1422G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC36A4	ENST00000326402.9	c.56-1422G>A		intron_variant		1	NM_152313.4	P1
SLC36A4	ENST00000529184.5	c.-321-1422G>A		intron_variant		2
SLC36A4	ENST00000524875.1	c.56-1422G>A		intron_variant, NMD_transcript_variant		3
SLC36A4	ENST00000527743.1	n.153-1422G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1876 AN: 152042 Hom.: 33 Cov.: 32

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.: 38 Cov.: 32 AF XY: 0.0122 AC XY: 908 AN XY: 74406

Gnomad4 AFR AF: 0.0434

Gnomad4 AMR AF: 0.00465

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00271 Hom.: 4

Bravo AF: 0.0145

Asia WGS AF: 0.00549 AC: 19 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
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs12296063; hg19: chr11-92920402;