17-19385207-T-A

Position:

• chr17-19385207-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000299610.5(MFAP4):​c.412A>T​(p.Asn138Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MFAP4 ENST00000299610.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0350

Genes affected

MFAP4 (HGNC:7035): (microfibril associated protein 4) This gene encodes a protein with similarity to a bovine microfibril-associated protein. The protein has binding specificities for both collagen and carbohydrate. It is thought to be an extracellular matrix protein which is involved in cell adhesion or intercellular interactions. The gene is located within the Smith-Magenis syndrome region. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

MFAP4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34473526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP4	NM_002404.3	c.412A>T	p.Asn138Tyr	missense_variant	5/6	ENST00000299610.5	NP_002395.1
MFAP4	NM_001198695.2	c.484A>T	p.Asn162Tyr	missense_variant	5/6		NP_001185624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP4	ENST00000299610.5	c.412A>T	p.Asn138Tyr	missense_variant	5/6	1	NM_002404.3	ENSP00000299610.5
MFAP4	ENST00000497081.6	c.487A>T	p.Asn163Tyr	missense_variant	4/5	1		ENSP00000468578.1
MFAP4	ENST00000395592.6	c.484A>T	p.Asn162Tyr	missense_variant	5/6	1		ENSP00000378957.2
MFAP4	ENST00000571210.1	n.523A>T		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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 26, 2022

The c.484A>T (p.N162Y) alteration is located in exon 5 (coding exon 5) of the MFAP4 gene. This alteration results from a A to T substitution at nucleotide position 484, causing the asparagine (N) at amino acid position 162 to be replaced by a tyrosine (Y). 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	0.24
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.7	.;.;M
MutationTaster	Benign	0.86	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.8	.;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.44
MutPred		0.43		.;.;Loss of ubiquitination at K143 (P = 0.0709);
MVP		0.22
MPC		1.4
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.59
gMVP		0.83

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: chr17-19288520;