13-40941101-A-C

Position:

• chr13-40941101-A-C

Variant summary

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

The NM_172373.4(ELF1):​c.1076T>G​(p.Val359Gly) 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. 15/21 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: 0.730

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=0.05861023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELF1	NM_172373.4	c.1076T>G	p.Val359Gly	missense_variant	8/9	ENST00000239882.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELF1	ENST00000239882.7	c.1076T>G	p.Val359Gly	missense_variant	8/9	1	NM_172373.4	P1
ELF1	ENST00000635415.1	c.1076T>G	p.Val359Gly	missense_variant	8/9	5
ELF1	ENST00000625359.1	c.1004T>G	p.Val335Gly	missense_variant	7/8	2
ELF1	ENST00000498824.4	c.*819T>G		3_prime_UTR_variant, NMD_transcript_variant	8/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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, 2022

The c.1076T>G (p.V359G) alteration is located in exon 8 (coding exon 7) of the ELF1 gene. This alteration results from a T to G substitution at nucleotide position 1076, causing the valine (V) at amino acid position 359 to be replaced by a glycine (G). 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	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.46	T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.67	N;.;.
MutationTaster	Benign	0.71	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N;.;.
REVEL	Benign	0.029
Sift	Benign	0.38	T;.;.
Sift4G	Benign	0.37	T;T;.
Polyphen		0.0	B;.;.
Vest4		0.15
MutPred		0.28		Gain of catalytic residue at K354 (P = 0.0112);.;Gain of catalytic residue at K354 (P = 0.0112);
MVP		0.16
MPC		0.21
ClinPred		0.038	T
GERP RS		-0.71
Varity_R		0.099
gMVP		0.44

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: chr13-41515237;