4-54064242-T-G

Position:

• chr4-54064242-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012110.4(CHIC2):​c.59A>C​(p.Glu20Ala) variant causes a missense change. 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: 33)
• Consequence: CHIC2 NM_012110.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73

Genes affected

CHIC2 (HGNC:1935): (cysteine rich hydrophobic domain 2) This gene encodes a member of the CHIC family of proteins. The encoded protein contains a cysteine-rich hydrophobic (CHIC) motif, and is localized to vesicular structures and the plasma membrane. This gene is associated with some cases of acute myeloid leukemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2977702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIC2	NM_012110.4	c.59A>C	p.Glu20Ala	missense_variant	1/6	ENST00000263921.8	NP_036242.1
CHIC2	XM_006714037.5	c.59A>C	p.Glu20Ala	missense_variant	1/6		XP_006714100.1
CHIC2	XM_011534382.3	c.59A>C	p.Glu20Ala	missense_variant	1/4		XP_011532684.1
CHIC2	XM_047450063.1	c.11+1062A>C		intron_variant			XP_047306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIC2	ENST00000263921.8	c.59A>C	p.Glu20Ala	missense_variant	1/6	1	NM_012110.4	ENSP00000263921	P1
CHIC2	ENST00000512964.5	c.59A>C	p.Glu20Ala	missense_variant	1/5	5		ENSP00000425238
CHIC2	ENST00000510894.1	c.59A>C	p.Glu20Ala	missense_variant	1/6	2		ENSP00000421032
CHIC2	ENST00000509678.1	n.67A>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.59A>C (p.E20A) alteration is located in exon 1 (coding exon 1) of the CHIC2 gene. This alteration results from a A to C substitution at nucleotide position 59, causing the glutamic acid (E) at amino acid position 20 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.46
Sift	Benign	0.15	T;D
Sift4G	Benign	0.23	T;T
Polyphen		0.88	P;.
Vest4		0.46
MutPred		0.20		Loss of disorder (P = 0.0342);Loss of disorder (P = 0.0342);
MVP		0.48
MPC		1.0
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.86

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: chr4-54930409;