chr4-6709317-T-G

Variant names:

• chr4-6709317-T-G
• NM_203462.3:c.313A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203462.3(MRFAP1L1):​c.313A>C​(p.Lys105Gln) 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. 15/20 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)
• Consequence: MRFAP1L1 NM_203462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.631

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

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=0.03457409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRFAP1L1	NM_203462.3	c.313A>C	p.Lys105Gln	missense_variant	Exon 1 of 2	ENST00000320848.7	NP_982287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRFAP1L1	ENST00000320848.7	c.313A>C	p.Lys105Gln	missense_variant	Exon 1 of 2	1	NM_203462.3	ENSP00000318154.6
MRFAP1L1	ENST00000500563.2	n.511A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.313A>C (p.K105Q) alteration is located in exon 1 (coding exon 1) of the MRFAP1L1 gene. This alteration results from a A to C substitution at nucleotide position 313, causing the lysine (K) at amino acid position 105 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.7
DANN	Benign	0.59
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.014
Sift	Benign	0.42	T
Sift4G	Benign	0.37	T
Polyphen		0.0030	B
Vest4		0.058
MutPred		0.21		Loss of ubiquitination at K105 (P = 0.0141);
MVP		0.13
MPC		0.91
ClinPred		0.14	T
GERP RS		-1.8
Varity_R		0.057
gMVP		0.016

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-6711044;