4-6709373-C-T

Variant names:

• chr4-6709373-C-T
• rs374512352
• NM_203462.3:c.257G>A

Variant summary

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

The NM_203462.3(MRFAP1L1):​c.257G>A​(p.Ser86Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MRFAP1L1 NM_203462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

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=0.024495333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRFAP1L1	NM_203462.3	c.257G>A	p.Ser86Asn	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.257G>A	p.Ser86Asn	missense_variant	Exon 1 of 2	1	NM_203462.3	ENSP00000318154.6
MRFAP1L1	ENST00000500563.2	n.455G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.11
DANN	Benign	0.79
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.024
Sift	Benign	0.60	T
Sift4G	Benign	0.081	T
Polyphen		0.0	B
Vest4		0.032
MutPred		0.23		Gain of glycosylation at S86 (P = 0.0894);
MVP		0.040
MPC		0.27
ClinPred		0.071	T
GERP RS		-5.2
Varity_R		0.036
gMVP		0.0094

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

Other links and lift over

dbSNP: rs374512352; hg19: chr4-6711100;