chr19-7670300-G-T

Variant names:

• chr19-7670300-G-T
• NM_020415.4:c.278G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020415.4(RETN):​c.278G>T​(p.Cys93Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,435,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RETN NM_020415.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

Genes affected

RETN (HGNC:20389): (resistin) This gene belongs to the family defined by the mouse resistin-like genes. The characteristic feature of this family is the C-terminal stretch of 10 cys residues with identical spacing. The mouse homolog of this protein is secreted by adipocytes, and may be the hormone potentially linking obesity to type II diabetes. The encoded protein also has an antimicrobial role in skin, displaying antibacterial activity against both Gram positive and Gram negative bacteria. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETN	NM_020415.4	c.278G>T	p.Cys93Phe	missense_variant	Exon 4 of 4	ENST00000221515.6	NP_065148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETN	ENST00000221515.6	c.278G>T	p.Cys93Phe	missense_variant	Exon 4 of 4	1	NM_020415.4	ENSP00000221515.1
RETN	ENST00000381324.2	c.200G>T	p.Cys67Phe	missense_variant	Exon 2 of 2	1		ENSP00000370725.2
RETN	ENST00000629642.1	c.200G>T	p.Cys67Phe	missense_variant	Exon 3 of 3	5		ENSP00000485998.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1435758 Hom.: 0 Cov.: 37 AF XY: 0.00000140 AC XY: 1 AN XY: 713170

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;D;.
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	-0.032	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-10	D;.;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0050	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.68
MutPred		0.95		Loss of disorder (P = 0.019);.;.;
MVP		0.82
MPC		1.3
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.82
gMVP		0.79

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: chr19-7735186;