rs374520604

chr19-29708291-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_031448.6(C19orf12):c.123C>T(p.Val41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: C19orf12 NM_031448.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.88

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-29708291-G-A is Benign according to our data. Variant chr19-29708291-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 537393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.88 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C19orf12	NM_031448.6	c.123C>T	p.Val41=	synonymous_variant	2/3	ENST00000323670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C19orf12	ENST00000323670.14	c.123C>T	p.Val41=	synonymous_variant	2/3	2	NM_031448.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248804 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461038 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726838

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 43 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 10, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.49
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs374520604; hg19: chr19-30199198; COSMIC: COSV100080622;