7-1744928-A-G

Variant names:

• chr7-1744928-A-G
• NM_001128636.4:c.332A>G

Variant summary

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

The NM_001128636.4(ELFN1):​c.332A>G​(p.Gln111Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELFN1 NM_001128636.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

Genes affected

ELFN1 (HGNC:33154): (extracellular leucine rich repeat and fibronectin type III domain containing 1) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in synapse organization. Predicted to be located in dendrite and excitatory synapse. Predicted to be active in extracellular matrix and extracellular space. [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 rank	MANE	Protein	UniProt
ELFN1	NM_001128636.4	c.332A>G	p.Gln111Arg	missense_variant	Exon 4 of 4	ENST00000424383.5	NP_001122108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELFN1	ENST00000424383.5	c.332A>G	p.Gln111Arg	missense_variant	Exon 4 of 4	5	NM_001128636.4	ENSP00000456548.1
ELFN1	ENST00000561626.4	c.332A>G	p.Gln111Arg	missense_variant	Exon 3 of 3	2		ENSP00000457193.1
ELFN1	ENST00000691883.1	c.332A>G	p.Gln111Arg	missense_variant	Exon 3 of 3			ENSP00000510296.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332A>G (p.Q111R) alteration is located in exon 2 (coding exon 1) of the ELFN1 gene. This alteration results from a A to G substitution at nucleotide position 332, causing the glutamine (Q) at amino acid position 111 to be replaced by an arginine (R). 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	0.20
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.68	.;T
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.65	D;D
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.7	D;D
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;D
Vest4		0.56
MVP		0.67
MPC		0.51
GERP RS		4.3
Varity_R		0.38
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: chr7-1784564;