chr19-17821377-G-T

Variant names:

• chr19-17821377-G-T
• rs1037546548
• NM_005543.4:c.130C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005543.4(INSL3):​c.130C>A​(p.Arg44Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: INSL3 NM_005543.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

Genes affected

INSL3 (HGNC:6086): (insulin like 3) This gene encodes a member of the insulin-like hormone superfamily. The encoded protein is mainly produced in gonadal tissues. Studies of the mouse counterpart suggest that this gene may be involved in the development of urogenital tract and female fertility. This protein may also act as a hormone to regulate growth and differentiation of gubernaculum, and thus mediating intra-abdominal testicular descent. Mutations in this gene may lead to cryptorchidism. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41808233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSL3	NM_005543.4	c.130C>A	p.Arg44Ser	missense_variant	Exon 1 of 2	ENST00000317306.8	NP_005534.2
INSL3	NM_001265587.2	c.130C>A	p.Arg44Ser	missense_variant	Exon 1 of 3		NP_001252516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSL3	ENST00000317306.8	c.130C>A	p.Arg44Ser	missense_variant	Exon 1 of 2	1	NM_005543.4	ENSP00000321724.6
INSL3	ENST00000379695.5	c.130C>A	p.Arg44Ser	missense_variant	Exon 1 of 3	1		ENSP00000369017.4
INSL3	ENST00000598577.1	c.127C>A	p.Arg43Ser	missense_variant	Exon 1 of 2	1		ENSP00000469309.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396124 Hom.: 0 Cov.: 64 AF XY: 0.00 AC XY: 0 AN XY: 688490

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;.
Eigen	Benign	0.082
Eigen_PC	Benign	-0.027
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.056	T;D
Polyphen		0.96	D;.
Vest4		0.43
MutPred		0.76		Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);
MVP		0.60
MPC		0.30
ClinPred		0.90	D
GERP RS		3.4
Varity_R		0.50
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1037546548; hg19: chr19-17932186;