7-1744958-G-C

Variant names:

• chr7-1744958-G-C
• rs965160942
• NM_001128636.4:c.362G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001128636.4(ELFN1):​c.362G>C​(p.Arg121Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R121H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ELFN1 NM_001128636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.56
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN1	NM_001128636.4	MANE Select	c.362G>C	p.Arg121Pro	missense	Exon 4 of 4	NP_001122108.1	P0C7U0
	ELFN1	NM_001394187.1		c.362G>C	p.Arg121Pro	missense	Exon 3 of 3	NP_001381116.1	P0C7U0
	ELFN1	NM_001394188.1		c.362G>C	p.Arg121Pro	missense	Exon 4 of 4	NP_001381117.1	P0C7U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN1	ENST00000424383.5	TSL:5 MANE Select	c.362G>C	p.Arg121Pro	missense	Exon 4 of 4	ENSP00000456548.1	P0C7U0
	ELFN1	ENST00000561626.4	TSL:2	c.362G>C	p.Arg121Pro	missense	Exon 3 of 3	ENSP00000457193.1	P0C7U0
	ELFN1	ENST00000691883.1		c.362G>C	p.Arg121Pro	missense	Exon 3 of 3	ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399040 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690074

African (AFR) AF: 0.00 AC: 0 AN: 31608

American (AMR) AF: 0.00 AC: 0 AN: 35722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35744

South Asian (SAS) AF: 0.00 AC: 0 AN: 79246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079038

Other (OTH) AF: 0.00 AC: 0 AN: 58012

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	D
M_CAP	Pathogenic	0.62	D
MetaRNN	Pathogenic	0.87	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	D
Sift	Uncertain	0.022	D
Sift4G	Benign	0.082	T
Polyphen		1.0	D
Vest4		0.75
MVP		0.84
MPC		0.95
GERP RS		4.3
Varity_R		0.53
gMVP		0.83
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs965160942; hg19: chr7-1784594;