4-6709362-C-T

Variant names:

• chr4-6709362-C-T
• rs199642592
• NM_203462.3:c.268G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203462.3(MRFAP1L1):​c.268G>A​(p.Asp90Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. 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. D90E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRFAP1L1 NM_203462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 0 publications found

Genes affected

MRFAP1L1 (HGNC:28796): (Morf4 family associated protein 1 like 1) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061526865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203462.3. 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
	MRFAP1L1	NM_203462.3	MANE Select	c.268G>A	p.Asp90Asn	missense	Exon 1 of 2	NP_982287.1	Q96HT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRFAP1L1	ENST00000320848.7	TSL:1 MANE Select	c.268G>A	p.Asp90Asn	missense	Exon 1 of 2	ENSP00000318154.6	Q96HT8
	MRFAP1L1	ENST00000906128.1		c.268G>A	p.Asp90Asn	missense	Exon 1 of 2	ENSP00000576187.1
	MRFAP1L1	ENST00000906129.1		c.268G>A	p.Asp90Asn	missense	Exon 1 of 2	ENSP00000576188.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.18
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.033
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.061	T
Polyphen		0.24	B
Vest4		0.13
MutPred		0.22		Gain of glycosylation at S94 (P = 0.012)
MVP		0.030
MPC		0.28
ClinPred		0.11	T
GERP RS		1.7
Varity_R		0.069
gMVP		0.027
Mutation Taster		=100/0	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: rs199642592; hg19: chr4-6711089;