rs45573936

Positions:

• chr6-44230625-T-C

Variant summary

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

The NM_001372327.1(SLC29A1):​c.647T>C​(p.Ile216Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0231 in 1,612,978 control chromosomes in the GnomAD database, including 511 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.016 (31 hom., cov: 32)
  • Exomes 𝑓: 0.024 (480 hom.)
• Consequence: SLC29A1 NM_001372327.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50

Genes affected

SLC29A1 (HGNC:11003): (solute carrier family 29 member 1 (Augustine blood group)) This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylthioinosine (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SLC29A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048289895).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (2489/151432) while in subpopulation NFE AF= 0.0257 (1747/67868). AF 95% confidence interval is 0.0247. There are 31 homozygotes in gnomad4. There are 1191 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2489 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A1	NM_001372327.1	c.647T>C	p.Ile216Thr	missense_variant	7/13	ENST00000371755.9	NP_001359256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC29A1	ENST00000371755.9	c.647T>C	p.Ile216Thr	missense_variant	7/13	1	NM_001372327.1	ENSP00000360820.3

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2490 AN: 151310 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00462

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.0142

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0150

GnomAD3 exomes AF: 0.0182 AC: 4566 AN: 251472 Hom.: 65 AF XY: 0.0186 AC XY: 2527 AN XY: 135912

Gnomad AFR exome AF: 0.00400

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0147

Gnomad FIN exome AF: 0.0239

Gnomad NFE exome AF: 0.0257

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0238 AC: 34779 AN: 1461546 Hom.: 480 Cov.: 35 AF XY: 0.0236 AC XY: 17187 AN XY: 727070

Gnomad4 AFR exome AF: 0.00358

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.00570

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.0261

Gnomad4 NFE exome AF: 0.0269

Gnomad4 OTH exome AF: 0.0223

GnomAD4 genome AF: 0.0164 AC: 2489 AN: 151432 Hom.: 31 Cov.: 32 AF XY: 0.0161 AC XY: 1191 AN XY: 73948

Gnomad4 AFR AF: 0.00465

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00462

Gnomad4 EAS AF: 0.000391

Gnomad4 SAS AF: 0.0138

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0148

Alfa AF: 0.0222 Hom.: 64

Bravo AF: 0.0151

TwinsUK AF: 0.0251 AC: 93

ALSPAC AF: 0.0252 AC: 97

ESP6500AA AF: 0.00409 AC: 18

ESP6500EA AF: 0.0298 AC: 256

ExAC AF: 0.0192 AC: 2328

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0214

EpiControl AF: 0.0220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D;.;D;D;.;D;D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;.;.;.;.;D;.;.
MetaRNN	Benign	0.0048	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.0	M;M;.;M;M;.;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N;N;.;N;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.21	T;T;.;T;T;T;T;T
Sift4G	Benign	0.34	T;T;.;T;T;T;T;T
Polyphen		0.96	D;D;.;D;D;.;D;D
Vest4		0.26
ClinPred		0.026	T
GERP RS		5.5
Varity_R		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs45573936; hg19: chr6-44198362; COSMIC: COSV99046102; COSMIC: COSV99046102;