3-38306349-C-A

Position:

• chr3-38306349-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001320033.2(SLC22A14):​c.323C>A​(p.Pro108His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,614,148 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (42 hom.)
• Consequence: SLC22A14 NM_001320033.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.95

Genes affected

SLC22A14 (HGNC:8495): (solute carrier family 22 member 14) This gene encodes a member of the organic-cation transporter family. It is located in a gene cluster with another member of the family, organic cation transporter like 3. The encoded protein is a transmembrane protein which is thought to transport small molecules and since this protein is conserved among several species, it is suggested to have a fundamental role in mammalian systems. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SLC22A14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004629612).
• BP6: Variant 3-38306349-C-A is Benign according to our data. Variant chr3-38306349-C-A is described in ClinVar as [Benign]. Clinvar id is 785043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2071/152266) while in subpopulation AFR AF= 0.0469 (1947/41536). AF 95% confidence interval is 0.0451. There are 46 homozygotes in gnomad4. There are 978 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A14	NM_001320033.2	c.323C>A	p.Pro108His	missense_variant	2/11	ENST00000448498.6	NP_001306962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A14	ENST00000448498.6	c.323C>A	p.Pro108His	missense_variant	2/11	1	NM_001320033.2	ENSP00000396283.1
SLC22A14	ENST00000273173.4	c.323C>A	p.Pro108His	missense_variant	1/10	1		ENSP00000273173.4
SLC22A14	ENST00000466887	c.-74C>A		5_prime_UTR_variant	2/4	4		ENSP00000442528.1
SLC22A14	ENST00000496724.1	n.1176C>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2068 AN: 152148 Hom.: 45 Cov.: 33

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00370 AC: 931 AN: 251474 Hom.: 23 AF XY: 0.00274 AC XY: 372 AN XY: 135910

Gnomad AFR exome AF: 0.0480

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00143 AC: 2088 AN: 1461882 Hom.: 42 Cov.: 32 AF XY: 0.00123 AC XY: 895 AN XY: 727244

Gnomad4 AFR exome AF: 0.0485

Gnomad4 AMR exome AF: 0.00340

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000908

Gnomad4 OTH exome AF: 0.00316

GnomAD4 genome AF: 0.0136 AC: 2071 AN: 152266 Hom.: 46 Cov.: 33 AF XY: 0.0131 AC XY: 978 AN XY: 74444

Gnomad4 AFR AF: 0.0469

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00272 Hom.: 12

Bravo AF: 0.0158

ESP6500AA AF: 0.0411 AC: 181

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00430 AC: 522

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.59	.;T
MetaRNN	Benign	0.0046	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;D
Vest4		0.39
MVP		0.46
MPC		0.59
ClinPred		0.035	T
GERP RS		4.7
Varity_R		0.23
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9847584; hg19: chr3-38347840;