chr4-169991557-C-G

Position:

• chr4-169991557-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021647.8(MFAP3L):​c.1051G>C​(p.Glu351Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MFAP3L NM_021647.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

Genes affected

MFAP3L (HGNC:29083): (microfibril associated protein 3 like) Located in several cellular components, including cell junction; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000249955 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12500912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP3L	NM_021647.8	c.1051G>C	p.Glu351Gln	missense_variant	3/3	ENST00000361618.4	NP_067679.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP3L	ENST00000361618.4	c.1051G>C	p.Glu351Gln	missense_variant	3/3	1	NM_021647.8	ENSP00000354583.3
MFAP3L	ENST00000393704.3	c.742G>C	p.Glu248Gln	missense_variant	2/2	1		ENSP00000377307.3
ENSG00000249955	ENST00000508955.2	n.298+1088C>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 03, 2024

The c.1051G>C (p.E351Q) alteration is located in exon 3 (coding exon 2) of the MFAP3L gene. This alteration results from a G to C substitution at nucleotide position 1051, causing the glutamic acid (E) at amino acid position 351 to be replaced by a glutamine (Q). 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	0.077
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.47
DEOGEN2	Benign	0.022	.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T;T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.29
Sift	Benign	0.34	.;T
Sift4G	Benign	0.50	T;T
Polyphen		0.077	.;B
Vest4		0.12
MutPred		0.10		.;Gain of glycosylation at T346 (P = 0.0324);
MVP		0.59
MPC		0.39
ClinPred		0.57	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.21

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: chr4-170912708;