1-75206671-A-G

Position:

• chr1-75206671-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152697.6(SLC44A5):​c.2096T>C​(p.Val699Ala) 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: 32)
• Consequence: SLC44A5 NM_152697.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

Genes affected

SLC44A5 (HGNC:28524): (solute carrier family 44 member 5) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A5	NM_001130058.2	c.2048-2838T>C		intron_variant		ENST00000370859.8	NP_001123530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A5	ENST00000370855.5	c.2096T>C	p.Val699Ala	missense_variant	24/24	1		ENSP00000359892.5
SLC44A5	ENST00000370859.8	c.2048-2838T>C		intron_variant		2	NM_001130058.2	ENSP00000359896.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Sep 30, 2024

The c.2096T>C (p.V699A) alteration is located in exon 24 (coding exon 23) of the SLC44A5 gene. This alteration results from a T to C substitution at nucleotide position 2096, causing the valine (V) at amino acid position 699 to be replaced by an alanine (A). 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0077
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.88		Gain of disorder (P = 0.0523);
MVP		0.11
MPC		0.32
ClinPred		0.91	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.72

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: chr1-75672356;