chr17-19387075-C-T

Variant names:

• chr17-19387075-C-T
• ENST00000395592.6:c.44G>A

Variant summary

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

The NM_001198695.2(MFAP4):​c.44G>A​(p.Gly15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MFAP4 NM_001198695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0840
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198695.2. 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.6+75G>A		intron	N/A	NP_002395.1	P55083-1
	MFAP4	NM_001198695.2		c.44G>A	p.Gly15Asp	missense	Exon 1 of 6	NP_001185624.1	P55083-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP4	ENST00000395592.6	TSL:1	c.44G>A	p.Gly15Asp	missense	Exon 1 of 6	ENSP00000378957.2	P55083-2
	MFAP4	ENST00000299610.5	TSL:1 MANE Select	c.6+75G>A		intron	N/A	ENSP00000299610.5	P55083-1
	MFAP4	ENST00000885623.1		c.6+75G>A		intron	N/A	ENSP00000555682.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451190 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 721836

African (AFR) AF: 0.00 AC: 0 AN: 33174

American (AMR) AF: 0.00 AC: 0 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25802

East Asian (EAS) AF: 0.00 AC: 0 AN: 39038

South Asian (SAS) AF: 0.00 AC: 0 AN: 86038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105446

Other (OTH) AF: 0.00 AC: 0 AN: 59650

GnomAD4 genome Cov.: 28

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	Benign	0.089
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.5
DANN	Uncertain	0.99
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.084
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.045
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.51
MutPred		0.32		Gain of helix (P = 0.027)
MVP		0.23
MPC		1.4
ClinPred		0.64	D
GERP RS		0.012
PromoterAI		0.040	Neutral
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.25		Position offset: -34

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

Other links and lift over

hg19: chr17-19290388;