rs11542419

Variant names:

• chr2-27207557-A-G
• rs11542419
• NM_021095.4:c.94T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021095.4(SLC5A6):​c.94T>C​(p.Phe32Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC5A6 NM_021095.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.28
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.94T>C	p.Phe32Leu	missense	Exon 3 of 17	NP_066918.2	Q9Y289
	SLC5A6	NR_028323.2		n.550T>C		non_coding_transcript_exon	Exon 3 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A6	ENST00000310574.8	TSL:1 MANE Select	c.94T>C	p.Phe32Leu	missense	Exon 3 of 17	ENSP00000310208.3	Q9Y289
	SLC5A6	ENST00000408041.5	TSL:1	c.94T>C	p.Phe32Leu	missense	Exon 4 of 18	ENSP00000384853.1	Q9Y289
	SLC5A6	ENST00000892752.1		c.94T>C	p.Phe32Leu	missense	Exon 3 of 17	ENSP00000562811.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.041
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.036	D
Polyphen		0.13	B
Vest4		0.70
MutPred		0.45		Loss of sheet (P = 0.0817)
MVP		0.38
MPC		0.65
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.78
Mutation Taster		=55/45	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: rs11542419; hg19: chr2-27430425;