1-202011297-C-A

Position:

• chr1-202011297-C-A

Variant summary

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

The NM_004433.5(ELF3):​c.161C>A​(p.Thr54Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: ELF3 NM_004433.5 missense, splice_region
• Scores: Splicing: ADA: 0.9044
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

Genes affected

ELF3 (HGNC:3318): (E74 like ETS transcription factor 3) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in inflammatory response; negative regulation of transcription, DNA-templated; and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF3	NM_004433.5	c.161C>A	p.Thr54Lys	missense_variant, splice_region_variant	2/9	ENST00000367284.10	NP_004424.3
ELF3	NM_001114309.2	c.161C>A	p.Thr54Lys	missense_variant, splice_region_variant	2/9		NP_001107781.1
ELF3	XM_005244942.4	c.161C>A	p.Thr54Lys	missense_variant, splice_region_variant	2/6		XP_005244999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF3	ENST00000367284.10	c.161C>A	p.Thr54Lys	missense_variant, splice_region_variant	2/9	1	NM_004433.5	ENSP00000356253	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 18, 2023

The c.161C>A (p.T54K) alteration is located in exon 2 (coding exon 1) of the ELF3 gene. This alteration results from a C to A substitution at nucleotide position 161, causing the threonine (T) at amino acid position 54 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.64	.;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	0.63	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.33
MutPred		0.53		Gain of ubiquitination at T54 (P = 0.0109);Gain of ubiquitination at T54 (P = 0.0109);Gain of ubiquitination at T54 (P = 0.0109);
MVP		0.45
MPC		0.54
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.20
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.90
dbscSNV1_RF	Pathogenic	0.81
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: -4

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: chr1-201980425;