5-140567630-C-A

Variant names:

• chr5-140567630-C-A
• rs761245053
• NM_080670.4:c.461C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080670.4(SLC35A4):​c.461C>A​(p.Ala154Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC35A4 NM_080670.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• 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 2 ACMG points.

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

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.461C>A	p.Ala154Asp	missense	Exon 3 of 3	NP_542401.1	Q96G79-1
	LOC131768270	NM_001394034.2	MANE Select	c.*868C>A		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.461C>A	p.Ala154Asp	missense	Exon 3 of 3	ENSP00000327133.3	Q96G79-1
	SLC35A4	ENST00000612662.2	TSL:1	c.461C>A	p.Ala154Asp	missense	Exon 3 of 3	ENSP00000479255.1	Q96G79-1
	ENSG00000293600	ENST00000715679.1	MANE Select	c.*868C>A		3_prime_UTR	Exon 3 of 3	ENSP00000520497.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251062 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.44
Sift	Benign	0.17	T
Sift4G	Uncertain	0.023	D
Polyphen		0.15	B
Vest4		0.64
MutPred		0.67		Gain of loop (P = 0.0121)
MVP		0.26
MPC		0.27
ClinPred		0.30	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.73
Mutation Taster		=84/16	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

dbSNP: rs761245053; hg19: chr5-139947215;