chr9-105244881-A-G

Position:

• chr9-105244881-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080546.5(SLC44A1):​c.13A>G​(p.Ser5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC44A1 NM_080546.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946

Genes affected

SLC44A1 (HGNC:18798): (solute carrier family 44 member 1) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]

LOC112268038 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04751572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A1	NM_080546.5	c.13A>G	p.Ser5Gly	missense_variant	1/16	ENST00000374720.8	NP_536856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A1	ENST00000374720.8	c.13A>G	p.Ser5Gly	missense_variant	1/16	1	NM_080546.5	ENSP00000363852.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1019538 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 481200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Apr 09, 2024

The c.13A>G (p.S5G) alteration is located in exon 1 (coding exon 1) of the SLC44A1 gene. This alteration results from a A to G substitution at nucleotide position 13, causing the serine (S) at amino acid position 5 to be replaced by a glycine (G). 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	Benign	0.049
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.50
DEOGEN2	Benign	0.0065	.;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.85	N;N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.56	N;N;N
REVEL	Benign	0.080
Sift	Benign	0.61	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.12
MutPred		0.18		Loss of phosphorylation at S5 (P = 0.0233);Loss of phosphorylation at S5 (P = 0.0233);Loss of phosphorylation at S5 (P = 0.0233);
MVP		0.11
MPC		0.30
ClinPred		0.068	T
GERP RS		2.7
Varity_R		0.12
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-108007162;