19-17489017-T-A

Position:

• chr19-17489017-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198580.3(SLC27A1):​c.896T>A​(p.Ile299Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC27A1 NM_198580.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87

Genes affected

SLC27A1 (HGNC:10995): (solute carrier family 27 member 1) Enables biotin transmembrane transporter activity; efflux transmembrane transporter activity; and long-chain fatty acid transporter activity. Involved in several processes, including carboxylic acid transmembrane transport; glycerophospholipid biosynthetic process; and lipid transport across blood-brain barrier. Located in membrane. Part of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PGLS-DT (HGNC:55274): (PGLS divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC27A1	NM_198580.3	c.896T>A	p.Ile299Asn	missense_variant	6/12	ENST00000252595.12	NP_940982.1
PGLS-DT	NR_147835.1	n.748A>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC27A1	ENST00000252595.12	c.896T>A	p.Ile299Asn	missense_variant	6/12	1	NM_198580.3	ENSP00000252595	P1
PGLS-DT	ENST00000596643.5	n.748A>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The c.896T>A (p.I299N) alteration is located in exon 6 (coding exon 6) of the SLC27A1 gene. This alteration results from a T to A substitution at nucleotide position 896, causing the isoleucine (I) at amino acid position 299 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	0.96	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.6	D;.
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.29	B;.
Vest4		0.76
MutPred		0.75		Loss of stability (P = 0.0074);.;
MVP		0.71
MPC		0.75
ClinPred		0.99	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.76
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17599826;