1-75214629-T-C

Position:

• chr1-75214629-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130058.2(SLC44A5):​c.1778A>G​(p.Asn593Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC44A5 NM_001130058.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.864

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20673043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A5	NM_001130058.2	c.1778A>G	p.Asn593Ser	missense_variant	20/24	ENST00000370859.8	NP_001123530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A5	ENST00000370859.8	c.1778A>G	p.Asn593Ser	missense_variant	20/24	2	NM_001130058.2	ENSP00000359896.3
SLC44A5	ENST00000370855.5	c.1778A>G	p.Asn593Ser	missense_variant	20/24	1		ENSP00000359892.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459600 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

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.: 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

Apr 13, 2023

The c.1778A>G (p.N593S) alteration is located in exon 20 (coding exon 19) of the SLC44A5 gene. This alteration results from a A to G substitution at nucleotide position 1778, causing the asparagine (N) at amino acid position 593 to be replaced by a serine (S). 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	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0093	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.14	N;N
REVEL	Benign	0.062
Sift	Benign	0.42	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.013	.;B
Vest4		0.075
MutPred		0.39		Loss of MoRF binding (P = 0.1135);Loss of MoRF binding (P = 0.1135);
MVP		0.20
MPC		0.20
ClinPred		0.20	T
GERP RS		4.1
Varity_R		0.044
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-75680314;