2-27201735-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021095.4(SLC5A6):c.1475G>A(p.Ser492Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,160 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 0.0066 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (13 hom.)
• Consequence: SLC5A6 NM_021095.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.931

Genes affected

SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002195239).
• BP6: Variant 2-27201735-C-T is Benign according to our data. Variant chr2-27201735-C-T is described in ClinVar as [Benign]. Clinvar id is 788951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00664 (1012/152306) while in subpopulation AFR AF= 0.0231 (960/41564). AF 95% confidence interval is 0.0219. There are 10 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A6	NM_021095.4	c.1475G>A	p.Ser492Asn	missense_variant	14/17	ENST00000310574.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A6	ENST00000310574.8	c.1475G>A	p.Ser492Asn	missense_variant	14/17	1	NM_021095.4	P1

Frequencies

GnomAD3 genomes AF: 0.00662 AC: 1007 AN: 152188 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00164 AC: 411 AN: 251368 Hom.: 7 AF XY: 0.00120 AC XY: 163 AN XY: 135850

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000736 AC: 1076 AN: 1461854 Hom.: 13 Cov.: 35 AF XY: 0.000605 AC XY: 440 AN XY: 727222

Gnomad4 AFR exome AF: 0.0279

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00664 AC: 1012 AN: 152306 Hom.: 10 Cov.: 32 AF XY: 0.00686 AC XY: 511 AN XY: 74494

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00153 Hom.: 6

Bravo AF: 0.00745

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00207 AC: 251

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	3.0
Dann	Benign	0.23
DEOGEN2	Benign	0.0057	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.077	N
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.95	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.14
Sift	Benign	0.54	T;T
Sift4G	Benign	0.63	T;T
Polyphen		0.0	B;B
Vest4		0.077
MVP		0.14
MPC		0.33
ClinPred		0.00064	T
GERP RS		-1.8
Varity_R		0.020
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs1064845; hg19: chr2-27424603; COSMIC: COSV99064626; COSMIC: COSV99064626;