NM_005478.6:c.119T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005478.6(INSL5):​c.119T>A​(p.Ile40Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,562 control chromosomes in the GnomAD database, including 1 homozygotes. 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. I40T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

INSL5
NM_005478.6 missense

Scores

12
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36
Variant links:
Genes affected
INSL5 (HGNC:6088): (insulin like 5) The protein encoded by this gene contains a classical signature of the insulin superfamily and is highly similar to relaxin 3 (RLN3/INSL7). [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INSL5NM_005478.6 linkc.119T>A p.Ile40Asn missense_variant Exon 1 of 2 ENST00000304526.3 NP_005469.2 Q9Y5Q6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INSL5ENST00000304526.3 linkc.119T>A p.Ile40Asn missense_variant Exon 1 of 2 1 NM_005478.6 ENSP00000302724.2 Q9Y5Q6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461562
Hom.:
1
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727130
show subpopulations
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.085
D
BayesDel_noAF
Benign
-0.12
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
D
Eigen
Benign
0.0048
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.64
T
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.64
D
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.37
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.015
D
Polyphen
0.94
P
Vest4
0.59
MutPred
0.31
Gain of MoRF binding (P = 0.104);
MVP
0.53
MPC
0.44
ClinPred
0.83
D
GERP RS
2.1
Varity_R
0.85
gMVP
0.69

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: chr1-67266786; API