rs202135938

Variant names:

• chr14-23275889-C-G
• rs202135938
• NM_020834.3:c.1339G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-23275889-C-G
• chr14-23275889-C-T

Variant summary

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

The NM_020834.3(HOMEZ):​c.1339G>C​(p.Glu447Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,448,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E447K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HOMEZ NM_020834.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80

Genes affected

HOMEZ (HGNC:20164): (homeobox and leucine zipper encoding) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15514073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMEZ	NM_020834.3	c.1339G>C	p.Glu447Gln	missense_variant	Exon 2 of 2	ENST00000357460.7	NP_065885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMEZ	ENST00000357460.7	c.1339G>C	p.Glu447Gln	missense_variant	Exon 2 of 2	1	NM_020834.3	ENSP00000350049.4
HOMEZ	ENST00000561013.3	c.1345G>C	p.Glu449Gln	missense_variant	Exon 3 of 3	2		ENSP00000453979.1
HOMEZ	ENST00000673724.1	c.1006G>C	p.Glu336Gln	missense_variant	Exon 3 of 3			ENSP00000501153.1
HOMEZ	ENST00000606731.2	c.829G>C	p.Glu277Gln	missense_variant	Exon 2 of 2	2		ENSP00000475307.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448690 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 719066

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: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0063	T;.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.23	N;N;.
REVEL	Benign	0.095
Sift	Uncertain	0.013	D;D;.
Sift4G	Benign	0.20	T;T;T
Polyphen		0.92	P;.;.
Vest4		0.18
MutPred		0.12		Loss of methylation at R448 (P = 0.1066);.;.;
MVP		0.28
MPC		0.77
ClinPred		0.46	T
GERP RS		5.8
Varity_R		0.098
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs202135938; hg19: chr14-23745098;