chr17-19387047-C-G

Position:

• chr17-19387047-C-G

Variant summary

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

The ENST00000299610.5(MFAP4):​c.6+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,249,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: MFAP4 ENST00000299610.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09258431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP4	NM_002404.3	c.6+103G>C		intron_variant		ENST00000299610.5	NP_002395.1
MFAP4	NM_001198695.2	c.72G>C	p.Leu24Phe	missense_variant	1/6		NP_001185624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP4	ENST00000395592.6	c.72G>C	p.Leu24Phe	missense_variant	1/6	1		ENSP00000378957.2
MFAP4	ENST00000299610.5	c.6+103G>C		intron_variant		1	NM_002404.3	ENSP00000299610.5
MFAP4	ENST00000571210.1	n.41+103G>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000560 AC: 7 AN: 1249750 Hom.: 0 Cov.: 32 AF XY: 0.00000969 AC XY: 6 AN XY: 619376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000615

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

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

Feb 13, 2024

The c.72G>C (p.L24F) alteration is located in exon 1 (coding exon 1) of the MFAP4 gene. This alteration results from a G to C substitution at nucleotide position 72, causing the leucine (L) at amino acid position 24 to be replaced by a phenylalanine (F). 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
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.0
DANN	Benign	0.89
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.18
Sift	Benign	0.18	T
Sift4G	Benign	0.093	T
Vest4		0.15
MutPred		0.47		Loss of helix (P = 0.0138);
MVP		0.20
MPC		0.48
ClinPred		0.39	T
GERP RS		3.9
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1913068218; hg19: chr17-19290360;