chr12-122208431-C-G

Variant names:

• chr12-122208431-C-G
• NM_001371333.1:c.670G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371333.1(DIABLO):​c.670G>C​(p.Gly224Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DIABLO NM_001371333.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

Genes affected

DIABLO (HGNC:21528): (diablo IAP-binding mitochondrial protein) This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and allows activation of caspases by binding to inhibitor of apoptosis proteins. Overexpression of the encoded protein sensitizes tumor cells to apoptosis. A mutation in this gene is associated with young-adult onset of nonsyndromic deafness-64. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

B3GNT4 (HGNC:15683): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase protein family. The encoded enzyme is involved in the biosynthesis of poly-N-acetyllactosamine chains and prefers lacto-N-neotetraose as a substrate. It is a type II transmembrane protein. [provided by RefSeq, Jul 2008]

ENSG00000256861 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.103797495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIABLO	NM_001371333.1	c.670G>C	p.Gly224Arg	missense_variant	Exon 6 of 6	ENST00000464942.7	NP_001358262.1
B3GNT4	NM_030765.4	c.*1043C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000324189.5	NP_110392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIABLO	ENST00000464942.7	c.670G>C	p.Gly224Arg	missense_variant	Exon 6 of 6	1	NM_001371333.1	ENSP00000442360.2
B3GNT4	ENST00000324189.5	c.*1043C>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_030765.4	ENSP00000319636.4
ENSG00000256861	ENST00000535844.1	n.*464G>C		non_coding_transcript_exon_variant	Exon 16 of 16	2		ENSP00000454454.1
ENSG00000256861	ENST00000535844.1	n.*464G>C		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000454454.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461584 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.25	T;T;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.78	T;T;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.20	N;.;N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.59	N;.;.;N
REVEL	Benign	0.091
Sift	Benign	0.15	T;.;.;T
Sift4G	Benign	0.41	T;T;.;T
Polyphen		0.0050	B;.;B;.
Vest4		0.11
MutPred		0.47		Gain of helix (P = 0.0496);.;Gain of helix (P = 0.0496);.;
MVP		0.71
MPC		0.036
ClinPred		0.057	T
GERP RS		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.068
gMVP		0.087

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122692978;