chr2-27201040-C-T

Variant names:

• chr2-27201040-C-T
• rs61737378
• NM_021095.4:c.1722G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_021095.4(SLC5A6):​c.1722G>A​(p.Pro574Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,613,772 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (12 hom., cov: 31)
  • Exomes 𝑓: 0.00075 (13 hom.)
• Consequence: SLC5A6 NM_021095.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.304
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• neurodegeneration, infantile-onset, biotin-responsive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• peripheral motor neuropathy, childhood-onset, biotin-responsive

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• inherited neurodegenerative disorder

  Inheritance: AR Classification: MODERATE Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-27201040-C-T is Benign according to our data. Variant chr2-27201040-C-T is described in ClinVar as Benign. ClinVar VariationId is 787001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.304 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00639 (973/152198) while in subpopulation AFR AF = 0.0221 (918/41510). AF 95% confidence interval is 0.0209. There are 12 homozygotes in GnomAd4. There are 479 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021095.4. 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
	SLC5A6	NM_021095.4	MANE Select	c.1722G>A	p.Pro574Pro	synonymous	Exon 16 of 17	NP_066918.2	Q9Y289
	SLC5A6	NR_028323.2		n.2530G>A		non_coding_transcript_exon	Exon 15 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A6	ENST00000310574.8	TSL:1 MANE Select	c.1722G>A	p.Pro574Pro	synonymous	Exon 16 of 17	ENSP00000310208.3	Q9Y289
	SLC5A6	ENST00000408041.5	TSL:1	c.1722G>A	p.Pro574Pro	synonymous	Exon 17 of 18	ENSP00000384853.1	Q9Y289
	SLC5A6	ENST00000892752.1		c.1755G>A	p.Pro585Pro	synonymous	Exon 16 of 17	ENSP00000562811.1

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 974 AN: 152080 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00190 AC: 476 AN: 251186 AF XY: 0.00130

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.000924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.000747 AC: 1092 AN: 1461574 Hom.: 13 Cov.: 31 AF XY: 0.000631 AC XY: 459 AN XY: 727082

African (AFR) AF: 0.0222 AC: 742 AN: 33476

American (AMR) AF: 0.00112 AC: 50 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26126

East Asian (EAS) AF: 0.000756 AC: 30 AN: 39700

South Asian (SAS) AF: 0.000766 AC: 66 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111850

Other (OTH) AF: 0.00189 AC: 114 AN: 60384

GnomAD4 genome AF: 0.00639 AC: 973 AN: 152198 Hom.: 12 Cov.: 31 AF XY: 0.00644 AC XY: 479 AN XY: 74402

African (AFR) AF: 0.0221 AC: 918 AN: 41510

American (AMR) AF: 0.00190 AC: 29 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68004

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00172 Hom.: 6

Bravo AF: 0.00730

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.2
DANN	Benign	0.45
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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: rs61737378; hg19: chr2-27423908;