NM_012243.3:c.531G>C

Variant names:

• chr1-100011430-G-C
• rs151009402
• NM_012243.3:c.531G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_012243.3(SLC35A3):​c.531G>C​(p.Met177Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000699 in 1,584,292 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00084 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (1 hom.)
• Consequence: SLC35A3 NM_012243.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.14
• Publications: 5 publications found

Genes affected

SLC35A3 (HGNC:11023): (solute carrier family 35 member A3) This gene encodes a UDP-N-acetylglucosamine transporter found in the golgi apparatus membrane. In cattle, a missense mutation in this gene causes complex vertebral malformation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SLC35A3 Gene-Disease associations (from GenCC):

• autism spectrum disorder - epilepsy - arthrogryposis syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

ENSG00000283761 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012751281).
• BP6: Variant 1-100011430-G-C is Benign according to our data. Variant chr1-100011430-G-C is described in ClinVar as Benign. ClinVar VariationId is 474762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012243.3. 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
	SLC35A3	NM_012243.3	MANE Select	c.531G>C	p.Met177Ile	missense	Exon 5 of 8	NP_036375.1	Q9Y2D2-1
	SLC35A3	NM_001271685.2		c.657G>C	p.Met219Ile	missense	Exon 5 of 8	NP_001258614.1	Q9Y2D2-2
	SLC35A3	NM_001438725.1		c.531G>C	p.Met177Ile	missense	Exon 6 of 9	NP_001425654.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A3	ENST00000533028.8	TSL:1 MANE Select	c.531G>C	p.Met177Ile	missense	Exon 5 of 8	ENSP00000433849.1	Q9Y2D2-1
	ENSG00000283761	ENST00000639037.1	TSL:5	c.531G>C	p.Met177Ile	missense	Exon 5 of 17	ENSP00000492745.1	A0A1W2PSA9
	SLC35A3	ENST00000638336.1	TSL:1	c.531G>C	p.Met177Ile	missense	Exon 5 of 6	ENSP00000491145.1	Q9Y2D2-3

Frequencies

GnomAD3 genomes AF: 0.000835 AC: 127 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000945 AC: 231 AN: 244396 AF XY: 0.000990

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.000155

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000752

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.000684 AC: 980 AN: 1432272 Hom.: 1 Cov.: 25 AF XY: 0.000707 AC XY: 504 AN XY: 713294

African (AFR) AF: 0.0000305 AC: 1 AN: 32834

American (AMR) AF: 0.000162 AC: 7 AN: 43190

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 305 AN: 25610

East Asian (EAS) AF: 0.00 AC: 0 AN: 39060

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82600

European-Finnish (FIN) AF: 0.0000950 AC: 5 AN: 52626

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5692

European-Non Finnish (NFE) AF: 0.000553 AC: 604 AN: 1091600

Other (OTH) AF: 0.000948 AC: 56 AN: 59060

GnomAD4 genome AF: 0.000835 AC: 127 AN: 152020 Hom.: 0 Cov.: 32 AF XY: 0.000768 AC XY: 57 AN XY: 74258

African (AFR) AF: 0.000121 AC: 5 AN: 41398

American (AMR) AF: 0.000262 AC: 4 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000947 AC: 1 AN: 10556

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

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 67990

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.00139 Hom.: 0

Bravo AF: 0.000884

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000939 AC: 114

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Autism spectrum disorder - epilepsy - arthrogryposis syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.65
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.096
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.44	N
PhyloP100		2.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.10
Sift	Benign	0.82	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.37		Gain of catalytic residue at M177 (P = 0.3387)
MVP		0.52
ClinPred		0.023	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.17
Mutation Taster		=62/37	polymorphism

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

Other links and lift over

dbSNP: rs151009402; hg19: chr1-100476986;