chr5-140567743-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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:0):

ENSG00000283155 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09304023).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080670.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A4	NM_080670.4	MANE Select	c.574C>G	p.Leu192Val	missense	Exon 3 of 3	NP_542401.1	Q96G79-1
	LOC131768270	NM_001394034.2	MANE Select	c.*981C>G		3_prime_UTR	Exon 3 of 3	NP_001380963.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A4	ENST00000323146.8	TSL:1 MANE Select	c.574C>G	p.Leu192Val	missense	Exon 3 of 3	ENSP00000327133.3	Q96G79-1
	SLC35A4	ENST00000612662.2	TSL:1	c.574C>G	p.Leu192Val	missense	Exon 3 of 3	ENSP00000479255.1	Q96G79-1
	ENSG00000293600	ENST00000715679.1	MANE Select	c.*981C>G		3_prime_UTR	Exon 3 of 3	ENSP00000520497.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.27	N
PhyloP100		2.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.062
Sift	Benign	0.69	T
Sift4G	Benign	1.0	T
Polyphen		0.068	B
Vest4		0.18
MutPred		0.48		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr5-139947328;