chr16-87831243-C-T

Variant names:

• chr16-87831243-C-T
• rs78174881
• NM_003486.7:c.*1727G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003486.7(SLC7A5):​c.*1727G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 152,420 control chromosomes in the GnomAD database, including 64 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 0.022 (64 hom., cov: 33)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: SLC7A5 NM_003486.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 6 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

SLC7A5-AS1 (HGNC:58301):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0222 (3378/152320) while in subpopulation NFE AF = 0.0337 (2290/68024). AF 95% confidence interval is 0.0325. There are 64 homozygotes in GnomAd4. There are 1673 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

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.*1727G>A		3_prime_UTR	Exon 10 of 10	NP_003477.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	ENST00000261622.5	TSL:1 MANE Select	c.*1727G>A		3_prime_UTR	Exon 10 of 10	ENSP00000261622.4	Q01650
	SLC7A5	ENST00000565644.6	TSL:1	c.*1727G>A		3_prime_UTR	Exon 10 of 10	ENSP00000454323.1	A0A0C4DGL4
	SLC7A5	ENST00000850914.1		c.*1727G>A		3_prime_UTR	Exon 10 of 10	ENSP00000520997.1	A0ABJ7H8K0

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3379 AN: 152202 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.00615

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0267

GnomAD4 exome AF: 0.0300 AC: 3 AN: 100 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 3 AN XY: 60

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0625 AC: 3 AN: 48

Other (OTH) AF: 0.00 AC: 0 AN: 16

GnomAD4 genome AF: 0.0222 AC: 3378 AN: 152320 Hom.: 64 Cov.: 33 AF XY: 0.0225 AC XY: 1673 AN XY: 74480

African (AFR) AF: 0.00613 AC: 255 AN: 41572

American (AMR) AF: 0.0302 AC: 462 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.0203 AC: 215 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0337 AC: 2290 AN: 68024

Other (OTH) AF: 0.0265 AC: 56 AN: 2116

Alfa AF: 0.0279 Hom.: 121

Bravo AF: 0.0221

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs78174881; hg19: chr16-87864849;