4-105897932-C-T

Variant names:

• chr4-105897932-C-T
• rs147630398
• NM_001033047.3:c.103C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001033047.3(NPNT):​c.103C>T​(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,592 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (8 hom.)
• Consequence: NPNT NM_001033047.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.22
• Publications: 0 publications found

Genes affected

NPNT (HGNC:27405): (nephronectin) Predicted to enable integrin binding activity. Predicted to be involved in several processes, including cell-cell adhesion mediated by integrin; positive regulation of ERK1 and ERK2 cascade; and positive regulation of osteoblast differentiation. Predicted to act upstream of or within positive regulation of transforming growth factor beta receptor signaling pathway. Located in extracellular exosome. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.124).
• BP6: Variant 4-105897932-C-T is Benign according to our data. Variant chr4-105897932-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2655004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.22 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033047.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPNT	NM_001033047.3	MANE Select	c.103C>T	p.Leu35Leu	synonymous	Exon 2 of 12	NP_001028219.1	Q6UXI9-1
	NPNT	NM_001184691.2		c.103C>T	p.Leu35Leu	synonymous	Exon 2 of 13	NP_001171620.1	Q6UXI9-3
	NPNT	NM_001184690.2		c.103C>T	p.Leu35Leu	synonymous	Exon 2 of 13	NP_001171619.1	Q6UXI9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPNT	ENST00000379987.7	TSL:1 MANE Select	c.103C>T	p.Leu35Leu	synonymous	Exon 2 of 12	ENSP00000369323.2	Q6UXI9-1
	NPNT	ENST00000305572.12	TSL:1	c.103C>T	p.Leu35Leu	synonymous	Exon 2 of 11	ENSP00000302557.8	Q6UXI9-2
	NPNT	ENST00000876321.1		c.103C>T	p.Leu35Leu	synonymous	Exon 2 of 14	ENSP00000546380.1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 165 AN: 151936 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00333

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00124

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00171 AC: 429 AN: 251198 AF XY: 0.00211

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00151

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00144 AC: 2102 AN: 1461538 Hom.: 8 Cov.: 30 AF XY: 0.00157 AC XY: 1140 AN XY: 727090

African (AFR) AF: 0.000269 AC: 9 AN: 33458

American (AMR) AF: 0.000828 AC: 37 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00643 AC: 168 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00477 AC: 411 AN: 86226

European-Finnish (FIN) AF: 0.000374 AC: 20 AN: 53416

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5766

European-Non Finnish (NFE) AF: 0.00118 AC: 1311 AN: 1111774

Other (OTH) AF: 0.00177 AC: 107 AN: 60376

GnomAD4 genome AF: 0.00108 AC: 164 AN: 152054 Hom.: 0 Cov.: 32 AF XY: 0.00108 AC XY: 80 AN XY: 74322

African (AFR) AF: 0.000362 AC: 15 AN: 41448

American (AMR) AF: 0.00150 AC: 23 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00333 AC: 16 AN: 4802

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10570

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00124 AC: 84 AN: 67986

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000732 Hom.: 0

Bravo AF: 0.00101

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.00214

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		1.2
PromoterAI		-0.022	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147630398; hg19: chr4-106819089;