chr1-100011430-G-C

Position:

• chr1-100011430-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 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. 14/21 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

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]

LOC124904230 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 id is 474762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35A3	NM_012243.3	c.531G>C	p.Met177Ile	missense_variant	5/8	ENST00000533028.8	NP_036375.1
LOC124904230	XR_007066249.1	n.279+26300C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028.8	c.531G>C	p.Met177Ile	missense_variant	5/8	1	NM_012243.3	ENSP00000433849	P1

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

GnomAD3 exomes AF: 0.000945 AC: 231 AN: 244396 Hom.: 0 AF XY: 0.000990 AC XY: 131 AN XY: 132320

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 SAS 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

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.000162

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.0000950

Gnomad4 NFE exome AF: 0.000553

Gnomad4 OTH exome AF: 0.000948

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

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000947

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.000958

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autism spectrum disorder - epilepsy - arthrogryposis syndrome Benign:2

Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Dec 06, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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;T;.;.;.;.;T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.096
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.013	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.44	.;N;N;.;N;.;.;N;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.64	.;.;N;.;.;.;.;N;.;.;.;.;.;N;.;.
REVEL	Benign	0.10
Sift	Benign	0.82	.;.;T;.;.;.;.;T;.;.;.;.;.;T;.;.
Sift4G	Benign	0.98	.;T;T;.;.;.;.;T;.;.;.;.;.;T;.;.
Polyphen		0.0	.;B;B;.;.;.;.;B;.;.;.;.;.;.;.;.
Vest4		0.26, 0.25, 0.27
MutPred		0.37		Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs151009402; hg19: chr1-100476986;