NM_018713.3:c.*397C>T

Variant names:

• chr1-219915052-G-A
• rs747429986
• NM_018713.3:c.*397C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018713.3(SLC30A10):​c.*397C>T variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC30A10 NM_018713.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.735
• Publications: 0 publications found

Genes affected

SLC30A10 (HGNC:25355): (solute carrier family 30 member 10) This gene is highly expressed in the liver and is inducible by manganese. Its protein product appears to be critical in maintaining manganese levels, and has higher specificity for manganese than zinc. Loss of function mutations appear to result in a pleomorphic phenotype, including dystonia and adult-onset parkinsonism. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

SLC30A10 Gene-Disease associations (from GenCC):

• cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018713.3. 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
	SLC30A10	NM_018713.3	MANE Select	c.*397C>T		3_prime_UTR	Exon 4 of 4	NP_061183.2
	SLC30A10	NM_001376929.1		c.*397C>T		3_prime_UTR	Exon 4 of 4	NP_001363858.1	A0A8Q3WLF3
	SLC30A10	NM_001416004.1		c.*397C>T		3_prime_UTR	Exon 3 of 3	NP_001402933.1	B3KR19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A10	ENST00000366926.4	TSL:1 MANE Select	c.*397C>T		3_prime_UTR	Exon 4 of 4	ENSP00000355893.4	Q6XR72-4
	SLC30A10	ENST00000356609.2	TSL:1	n.*1221C>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000349018.2	Q6XR72-3
	SLC30A10	ENST00000484079.1	TSL:1	n.1673C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 13026 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6528

African (AFR) AF: 0.00 AC: 0 AN: 322

American (AMR) AF: 0.00 AC: 0 AN: 1738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 380

East Asian (EAS) AF: 0.00 AC: 0 AN: 520

South Asian (SAS) AF: 0.00 AC: 0 AN: 736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 30

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8246

Other (OTH) AF: 0.00 AC: 0 AN: 656

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hypermanganesemia with dystonia, polycythemia, and cirrhosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.8
DANN	Benign	0.78
PhyloP100		-0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747429986; hg19: chr1-220088394;