5-140567362-T-G

Variant names:

• chr5-140567362-T-G
• rs147478659
• NM_080670.4:c.193T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080670.4(SLC35A4):​c.193T>G​(p.Cys65Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C65S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC35A4 NM_080670.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35120898).

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.193T>G	p.Cys65Gly	missense	Exon 3 of 3	NP_542401.1	Q96G79-1
	LOC131768270	NM_001394034.2	MANE Select	c.*600T>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.193T>G	p.Cys65Gly	missense	Exon 3 of 3	ENSP00000327133.3	Q96G79-1
	SLC35A4	ENST00000612662.2	TSL:1	c.193T>G	p.Cys65Gly	missense	Exon 3 of 3	ENSP00000479255.1	Q96G79-1
	ENSG00000293600	ENST00000715679.1	MANE Select	c.*600T>G		3_prime_UTR	Exon 3 of 3	ENSP00000520497.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0225104), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Benign	0.47	T
Sift4G	Benign	0.064	T
Polyphen		0.075	B
Vest4		0.49
MutPred		0.69		Loss of stability (P = 0.0145)
MVP		0.62
MPC		0.17
ClinPred		0.45	T
GERP RS		5.2
Varity_R		0.25
gMVP		0.52
Mutation Taster		=77/23	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: rs147478659; hg19: chr5-139946947;