17-19386838-C-T

Variant names:

• chr17-19386838-C-T
• rs1451662039
• ENST00000497081.6:c.82G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002404.3(MFAP4):​c.7G>A​(p.Ala3Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 1,559,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. A3S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: MFAP4 NM_002404.3 missense, splice_region
• Scores: Splicing: ADA: 0.9055
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13069907).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002404.3. 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
	MFAP4	NM_002404.3	MANE Select	c.7G>A	p.Ala3Thr	missense splice_region	Exon 2 of 6	NP_002395.1	P55083-1
	MFAP4	NM_001198695.2		c.79G>A	p.Ala27Thr	missense splice_region	Exon 2 of 6	NP_001185624.1	P55083-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP4	ENST00000497081.6	TSL:1	c.82G>A	p.Ala28Thr	missense	Exon 1 of 5	ENSP00000468578.1	K7ES70
	MFAP4	ENST00000299610.5	TSL:1 MANE Select	c.7G>A	p.Ala3Thr	missense splice_region	Exon 2 of 6	ENSP00000299610.5	P55083-1
	MFAP4	ENST00000395592.6	TSL:1	c.79G>A	p.Ala27Thr	missense splice_region	Exon 2 of 6	ENSP00000378957.2	P55083-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000617 AC: 1 AN: 162058 AF XY: 0.00

Gnomad AFR exome AF: 0.000115

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000782 AC: 11 AN: 1407194 Hom.: 0 Cov.: 31 AF XY: 0.00000576 AC XY: 4 AN XY: 694890

African (AFR) AF: 0.000156 AC: 5 AN: 32030

American (AMR) AF: 0.00 AC: 0 AN: 36412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 36396

South Asian (SAS) AF: 0.00 AC: 0 AN: 79796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49488

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

European-Non Finnish (NFE) AF: 0.00000554 AC: 6 AN: 1083856

Other (OTH) AF: 0.00 AC: 0 AN: 58330

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74316

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.63
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.053
Sift	Benign	0.31	T
Sift4G	Benign	0.15	T
Polyphen		0.028	B
Vest4		0.15
MutPred		0.22		Gain of loop (P = 0.0195)
MVP		0.11
MPC		0.80
ClinPred		0.26	T
GERP RS		4.0
PromoterAI		-0.0040	Neutral
Varity_R		0.15
gMVP		0.45
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.030		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: rs1451662039; hg19: chr17-19290151;