rs10424582

Variant names:

• chr19-29702814-G-A
• rs10424582
• NM_031448.6:c.324C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-29702814-G-A
• chr19-29702814-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000323670.14(C19orf12):​c.324C>T​(p.Thr108Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,613,648 control chromosomes in the GnomAD database, including 430,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39475 hom., cov: 31)
  • Exomes 𝑓: 0.73 (391083 hom.)
• Consequence: C19orf12 ENST00000323670.14 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.126
• Publications: 18 publications found

Genes affected

C19orf12 (HGNC:25443): (chromosome 19 open reading frame 12) This gene encodes a small transmembrane protein. Mutations in this gene are a cause of neurodegeneration with brain iron accumulation-4 (NBIA4), but the specific function of the encoded protein is unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

C19orf12 Gene-Disease associations (from GenCC):

• neurodegeneration with brain iron accumulation 4

  Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Illumina, Ambry Genetics, G2P
• hereditary spastic paraplegia 43

  Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-29702814-G-A is Benign according to our data. Variant chr19-29702814-G-A is described in ClinVar as Benign. ClinVar VariationId is 128537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.126 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000323670.14. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf12	NM_031448.6	MANE Select	c.324C>T	p.Thr108Thr	synonymous	Exon 3 of 3	NP_113636.2
	C19orf12	NM_001031726.4		c.324C>T	p.Thr108Thr	synonymous	Exon 3 of 3	NP_001026896.3
	C19orf12	NM_001256047.2		c.324C>T	p.Thr108Thr	synonymous	Exon 3 of 3	NP_001242976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf12	ENST00000323670.14	TSL:2 MANE Select	c.324C>T	p.Thr108Thr	synonymous	Exon 3 of 3	ENSP00000313332.9
	C19orf12	ENST00000392276.1	TSL:1	c.132C>T	p.Thr44Thr	synonymous	Exon 2 of 2	ENSP00000376102.1
	C19orf12	ENST00000592153.5	TSL:1	c.291-22C>T		intron	N/A	ENSP00000467117.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108254 AN: 151922 Hom.: 39453 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.698

GnomAD2 exomes AF: 0.655 AC: 164452 AN: 251040 AF XY: 0.665

Gnomad AFR exome AF: 0.777

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.737

Gnomad EAS exome AF: 0.302

Gnomad FIN exome AF: 0.653

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.679

GnomAD4 exome AF: 0.725 AC: 1060037 AN: 1461608 Hom.: 391083 Cov.: 83 AF XY: 0.724 AC XY: 526598 AN XY: 727054

African (AFR) AF: 0.776 AC: 25973 AN: 33476

American (AMR) AF: 0.466 AC: 20859 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 19207 AN: 26134

East Asian (EAS) AF: 0.308 AC: 12232 AN: 39688

South Asian (SAS) AF: 0.648 AC: 55912 AN: 86256

European-Finnish (FIN) AF: 0.661 AC: 35254 AN: 53310

Middle Eastern (MID) AF: 0.712 AC: 4106 AN: 5768

European-Non Finnish (NFE) AF: 0.759 AC: 843518 AN: 1111876

Other (OTH) AF: 0.712 AC: 42976 AN: 60386

GnomAD4 genome AF: 0.712 AC: 108319 AN: 152040 Hom.: 39475 Cov.: 31 AF XY: 0.699 AC XY: 51956 AN XY: 74324

African (AFR) AF: 0.775 AC: 32162 AN: 41490

American (AMR) AF: 0.574 AC: 8766 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2535 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1559 AN: 5136

South Asian (SAS) AF: 0.632 AC: 3049 AN: 4822

European-Finnish (FIN) AF: 0.641 AC: 6782 AN: 10574

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51107 AN: 67954

Other (OTH) AF: 0.699 AC: 1472 AN: 2106

Alfa AF: 0.738 Hom.: 31682

Bravo AF: 0.708

Asia WGS AF: 0.510 AC: 1775 AN: 3478

EpiCase AF: 0.746

EpiControl AF: 0.746

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Neurodegeneration with brain iron accumulation 4 (5)
-	-	3	not specified (3)
-	-	2	Hereditary spastic paraplegia 43 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Benign	0.64
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs10424582; hg19: chr19-30193721; COSMIC: COSV60364385; COSMIC: COSV60364385;