NM_003486.7:c.1043+6C>T

Variant names:

• chr16-87838708-G-A
• rs33966404
• NM_003486.7:c.1043+6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003486.7(SLC7A5):​c.1043+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,609,204 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (65 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (55 hom.)
• Consequence: SLC7A5 NM_003486.7 splice_region, intron
• Scores: Splicing: ADA: 0.00001699
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.58
• Publications: 0 publications found

Genes affected

SLC7A5 (HGNC:11063): (solute carrier family 7 member 5) Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical plasma membrane; and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-87838708-G-A is Benign according to our data. Variant chr16-87838708-G-A is described in ClinVar as Benign. ClinVar VariationId is 781231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003486.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	NM_003486.7	MANE Select	c.1043+6C>T		splice_region intron	N/A	NP_003477.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	ENST00000261622.5	TSL:1 MANE Select	c.1043+6C>T		splice_region intron	N/A	ENSP00000261622.4	Q01650
	SLC7A5	ENST00000565644.6	TSL:1	c.245+6C>T		splice_region intron	N/A	ENSP00000454323.1	A0A0C4DGL4
	SLC7A5	ENST00000850914.1		c.1097+6C>T		splice_region intron	N/A	ENSP00000520997.1	A0ABJ7H8K0

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2712 AN: 152226 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00463 AC: 1163 AN: 251050 AF XY: 0.00324

Gnomad AFR exome AF: 0.0620

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00183 AC: 2663 AN: 1456860 Hom.: 55 Cov.: 30 AF XY: 0.00154 AC XY: 1118 AN XY: 725112

African (AFR) AF: 0.0636 AC: 2124 AN: 33380

American (AMR) AF: 0.00400 AC: 179 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53152

Middle Eastern (MID) AF: 0.00313 AC: 18 AN: 5756

European-Non Finnish (NFE) AF: 0.0000758 AC: 84 AN: 1107696

Other (OTH) AF: 0.00402 AC: 242 AN: 60204

GnomAD4 genome AF: 0.0178 AC: 2716 AN: 152344 Hom.: 65 Cov.: 32 AF XY: 0.0174 AC XY: 1295 AN XY: 74484

African (AFR) AF: 0.0617 AC: 2564 AN: 41564

American (AMR) AF: 0.00751 AC: 115 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68032

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00754 Hom.: 18

Bravo AF: 0.0199

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.045
DANN	Benign	0.77
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs33966404; hg19: chr16-87872314;