5-140567743-C-G

Variant names:

• chr5-140567743-C-G
• NM_080670.4:c.574C>G

Variant summary

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

The NM_080670.4(SLC35A4):​c.574C>G​(p.Leu192Val) 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. 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: 33)
• Consequence: SLC35A4 NM_080670.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

Genes affected

SLC35A4 (HGNC:20753): (solute carrier family 35 member A4) Predicted to enable pyrimidine nucleotide-sugar transmembrane transporter activity. Involved in positive regulation of translation in response to stress. Predicted to be located in Golgi apparatus. Predicted to be integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC131768270 (HGNC:):

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=0.09304023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A4	NM_080670.4	c.574C>G	p.Leu192Val	missense_variant	Exon 3 of 3	ENST00000323146.8	NP_542401.1
LOC131768270	NM_001394034.2	c.*981C>G		3_prime_UTR_variant	Exon 3 of 3		NP_001380963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A4	ENST00000323146.8	c.574C>G	p.Leu192Val	missense_variant	Exon 3 of 3	1	NM_080670.4	ENSP00000327133.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.574C>G (p.L192V) alteration is located in exon 3 (coding exon 1) of the SLC35A4 gene. This alteration results from a C to G substitution at nucleotide position 574, causing the leucine (L) at amino acid position 192 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.056	T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	.;T;.
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.27	N;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.73	N;.;N
REVEL	Benign	0.062
Sift	Benign	0.69	T;.;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.068	B;B;B
Vest4		0.18
MutPred		0.48		Gain of catalytic residue at L192 (P = 0.1395);Gain of catalytic residue at L192 (P = 0.1395);Gain of catalytic residue at L192 (P = 0.1395);
MVP		0.040
MPC		0.53
ClinPred		0.51	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.27

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: chr5-139947328;