1-205616626-T-A

Position:

• chr1-205616626-T-A

Variant summary

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

The NM_001973.4(ELK4):​c.1216A>T​(p.Ser406Cys) variant causes a missense 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: ELK4 NM_001973.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07

Genes affected

ELK4 (HGNC:3326): (ETS transcription factor ELK4) This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum reponse element in the promoter of the c-fos proto-oncogene. The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. Several transcript variants have been described for this gene. [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=0.3004946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELK4	NM_001973.4	c.1216A>T	p.Ser406Cys	missense_variant	5/5	ENST00000357992.9	NP_001964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELK4	ENST00000357992.9	c.1216A>T	p.Ser406Cys	missense_variant	5/5	1	NM_001973.4	ENSP00000350681.4
ELK4	ENST00000616704.4	n.1216A>T		non_coding_transcript_exon_variant	5/10	2		ENSP00000483628.1

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

Aug 30, 2021

The c.1216A>T (p.S406C) alteration is located in exon 5 (coding exon 4) of the ELK4 gene. This alteration results from a A to T substitution at nucleotide position 1216, causing the serine (S) at amino acid position 406 to be replaced by a cysteine (C). 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	0.11
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.090
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.027	D
Polyphen		0.98	D
Vest4		0.39
MutPred		0.26		Loss of disorder (P = 0.0044);
MVP		0.58
MPC		0.40
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.34

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: chr1-205585754;