Variant 4-6709613-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_203462.3(MRFAP1L1):c.17T>A(p.Ile6Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,460,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MRFAP1L1
NM_203462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.325

Variant links:

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]

MRFAP1L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042383313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRFAP1L1	NM_203462.3 linkuse as main transcript	c.17T>A	p.Ile6Lys	missense_variant	1/2	ENST00000320848.7	NP_982287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRFAP1L1	ENST00000320848.7 linkuse as main transcript	c.17T>A	p.Ile6Lys	missense_variant	1/2	1	NM_203462.3	ENSP00000318154	P1
MRFAP1L1	ENST00000500563.2 linkuse as main transcript	n.215T>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250212

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1460738

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726392

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.17T>A (p.I6K) alteration is located in exon 1 (coding exon 1) of the MRFAP1L1 gene. This alteration results from a T to A substitution at nucleotide position 17, causing the isoleucine (I) at amino acid position 6 to be replaced by a lysine (K). 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

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.046

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.70

M_CAP

Benign

0.0023

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.4

REVEL

Benign

0.0030

Sift

Benign

0.066

Sift4G

Benign

0.11

Polyphen

0.012

Vest4

0.20

MutPred

0.25

Gain of solvent accessibility (P = 0.0068);

MVP

0.16

MPC

0.52

ClinPred

0.026

GERP RS

-3.9

Varity_R

0.060

gMVP

0.059

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over