NM_002404.3:c.203T>C

Variant names:

• chr17-19386347-A-G
• rs1913031234
• NM_002404.3:c.203T>C

Variant summary

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

The NM_002404.3(MFAP4):​c.203T>C​(p.Val68Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,612,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: MFAP4 NM_002404.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

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.203T>C	p.Val68Ala	missense	Exon 3 of 6	NP_002395.1	P55083-1
	MFAP4	NM_001198695.2		c.275T>C	p.Val92Ala	missense	Exon 3 of 6	NP_001185624.1	P55083-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP4	ENST00000299610.5	TSL:1 MANE Select	c.203T>C	p.Val68Ala	missense	Exon 3 of 6	ENSP00000299610.5	P55083-1
	MFAP4	ENST00000497081.6	TSL:1	c.278T>C	p.Val93Ala	missense	Exon 2 of 5	ENSP00000468578.1	K7ES70
	MFAP4	ENST00000395592.6	TSL:1	c.275T>C	p.Val92Ala	missense	Exon 3 of 6	ENSP00000378957.2	P55083-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152036 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460378 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726454

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111392

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152036 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	1.9	L
PhyloP100		6.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.4	D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.024	D
Sift4G	Benign	0.062	T
Polyphen		0.99	D
Vest4		0.87
MutPred		0.72		Gain of sheet (P = 0.1945)
MVP		0.80
MPC		1.3
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.72
Mutation Taster		=60/40	polymorphism

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: rs1913031234; hg19: chr17-19289660;