2-27201104-C-T

Position:

• chr2-27201104-C-T

Variant summary

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

The NM_021095.4(SLC5A6):​c.1658G>A​(p.Arg553Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,611,090 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (7 hom.)
• Consequence: SLC5A6 NM_021095.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.756

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]

SLC5A6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077798665).
• BP6: Variant 2-27201104-C-T is Benign according to our data. Variant chr2-27201104-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00208 (317/152174) while in subpopulation AMR AF= 0.00353 (54/15290). AF 95% confidence interval is 0.00278. There are 1 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A6	NM_021095.4	c.1658G>A	p.Arg553Gln	missense_variant	16/17	ENST00000310574.8	NP_066918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A6	ENST00000310574.8	c.1658G>A	p.Arg553Gln	missense_variant	16/17	1	NM_021095.4	ENSP00000310208.3

Frequencies

GnomAD3 genomes AF: 0.00208 AC: 317 AN: 152056 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00547

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.00219 AC: 548 AN: 250030 Hom.: 3 AF XY: 0.00210 AC XY: 284 AN XY: 135056

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000727

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.00950

Gnomad NFE exome AF: 0.00249

Gnomad OTH exome AF: 0.00395

GnomAD4 exome AF: 0.00220 AC: 3210 AN: 1458916 Hom.: 7 Cov.: 31 AF XY: 0.00222 AC XY: 1613 AN XY: 725796

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000763

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00967

Gnomad4 NFE exome AF: 0.00223

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00208 AC: 317 AN: 152174 Hom.: 1 Cov.: 31 AF XY: 0.00210 AC XY: 156 AN XY: 74400

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00547

Gnomad4 NFE AF: 0.00275

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.00207 Hom.: 1

Bravo AF: 0.00168

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00256 AC: 22

ExAC AF: 0.00192 AC: 233

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00278

EpiControl AF: 0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 01, 2018	- -

Neurodegeneration, infantile-onset, biotin-responsive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.0078	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.87	N;N
REVEL	Benign	0.069
Sift	Benign	0.061	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.40	B;B
Vest4		0.21
MVP		0.33
MPC		0.42
ClinPred		0.044	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141244089; hg19: chr2-27423972; COSMIC: COSV60160798; COSMIC: COSV60160798;