13-40941240-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172373.4(ELF1):c.937C>T(p.Pro313Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELF1 NM_172373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.803

Genes affected

ELF1 (HGNC:3316): (E74 like ETS transcription factor 1) This gene encodes an E26 transformation-specific related transcription factor. The encoded protein is primarily expressed in lymphoid cells and acts as both an enhancer and a repressor to regulate transcription of various genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057011962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELF1	NM_172373.4	c.937C>T	p.Pro313Ser	missense_variant	8/9	ENST00000239882.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELF1	ENST00000239882.7	c.937C>T	p.Pro313Ser	missense_variant	8/9	1	NM_172373.4	P1
ELF1	ENST00000635415.1	c.937C>T	p.Pro313Ser	missense_variant	8/9	5
ELF1	ENST00000625359.1	c.865C>T	p.Pro289Ser	missense_variant	7/8	2
ELF1	ENST00000498824.4	c.*680C>T		3_prime_UTR_variant, NMD_transcript_variant	8/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Jan 17, 2023

The c.937C>T (p.P313S) alteration is located in exon 8 (coding exon 7) of the ELF1 gene. This alteration results from a C to T substitution at nucleotide position 937, causing the proline (P) at amino acid position 313 to be replaced by a serine (S). 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	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	12
Dann	Benign	0.76
DEOGEN2	Benign	0.046	T;.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.090	N;.;.
REVEL	Benign	0.019
Sift	Benign	0.12	T;.;.
Sift4G	Benign	0.46	T;T;.
Polyphen		0.0020	B;.;.
Vest4		0.088
MutPred		0.34		Gain of phosphorylation at P313 (P = 0.0017);.;Gain of phosphorylation at P313 (P = 0.0017);
MVP		0.19
MPC		0.16
ClinPred		0.12	T
GERP RS		3.5
Varity_R		0.023
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr13-41515376; COSMIC: COSV99523013;