NM_003060.4:c.-77G>A

Variant names:

• chr5-132369896-G-A
• rs13180295
• NM_003060.4:c.-77G>A

Variant summary

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

The NM_003060.4(SLC22A5):​c.-77G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 1,563,670 control chromosomes in the GnomAD database, including 6,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (576 hom., cov: 33)
  • Exomes 𝑓: 0.079 (5571 hom.)
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.425
• Publications: 12 publications found

Genes affected

SLC22A5 (HGNC:10969): (solute carrier family 22 member 5) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-132369896-G-A is Benign according to our data. Variant chr5-132369896-G-A is described in ClinVar as Benign. ClinVar VariationId is 25343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003060.4. 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
	SLC22A5	NM_003060.4	MANE Select	c.-77G>A		5_prime_UTR	Exon 1 of 10	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.-77G>A		5_prime_UTR	Exon 1 of 11	NP_001295051.1	O76082-3
	MIR3936HG	NR_110997.1		n.21C>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.-77G>A		5_prime_UTR	Exon 1 of 10	ENSP00000245407.3	O76082-1
	SLC22A5	ENST00000435065.7	TSL:1	c.-77G>A		5_prime_UTR	Exon 1 of 11	ENSP00000402760.2	O76082-3
	SLC22A5	ENST00000448810.6	TSL:1	n.-77G>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000401860.2	H7C1R8

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11686 AN: 152136 Hom.: 579 Cov.: 33

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.0794 AC: 112084 AN: 1411424 Hom.: 5571 Cov.: 30 AF XY: 0.0789 AC XY: 55178 AN XY: 699548

African (AFR) AF: 0.0597 AC: 1918 AN: 32114

American (AMR) AF: 0.0374 AC: 1423 AN: 38034

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2733 AN: 23972

East Asian (EAS) AF: 0.295 AC: 11390 AN: 38570

South Asian (SAS) AF: 0.0539 AC: 4350 AN: 80646

European-Finnish (FIN) AF: 0.0769 AC: 3480 AN: 45236

Middle Eastern (MID) AF: 0.0672 AC: 278 AN: 4134

European-Non Finnish (NFE) AF: 0.0750 AC: 81741 AN: 1090476

Other (OTH) AF: 0.0819 AC: 4771 AN: 58242

GnomAD4 genome AF: 0.0768 AC: 11685 AN: 152246 Hom.: 576 Cov.: 33 AF XY: 0.0759 AC XY: 5645 AN XY: 74418

African (AFR) AF: 0.0617 AC: 2566 AN: 41564

American (AMR) AF: 0.0494 AC: 756 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1386 AN: 5162

South Asian (SAS) AF: 0.0648 AC: 313 AN: 4830

European-Finnish (FIN) AF: 0.0748 AC: 793 AN: 10608

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0767 AC: 5216 AN: 67992

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0763 Hom.: 63

Bravo AF: 0.0746

Asia WGS AF: 0.124 AC: 429 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Renal carnitine transport defect (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.6
DANN	Benign	0.82
PhyloP100		-0.42
PromoterAI		-0.41	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	polymorphism (auto)

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: rs13180295; hg19: chr5-131705588;